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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-003502-24 | EudraCT Number |
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The objective of this study is to compare the progression free survival (PFS), overall survival (OS), objective response rate (ORR), time to treatment failure (TTF), duration of response (DoR), quality of life, safety and tolerability of tivozanib in combination with mFOLFOX6 and bevacizumab in combination with mFOLFOX6.
Imaging scans (computed tomography [CT]/magnetic resonance imaging [MRI]) to assess disease progression were to be completed within 28 days prior to first study drug administration, approximately every 8 weeks for the first 18 months and then approximately every 12 weeks until the patient showed progressive disease (PD) per the investigator, withdrew consent, was lost to follow-up or died. Per the original protocol, all patients were to be contacted by the study site every 12 weeks for survival following the end-of-treatment visit until death or for no more than 3 years after the end-of-treatment visit.
The interim futility analysis was conducted in December 2013, based on a pre-specified analysis cutoff date of 13 September 2013. The study was brought to a close as specified in the protocol due to the results of the interim futility analysis and only those participants who were deriving benefit (per the treating physician) from their current treatment remained on study until one of the discontinuation criteria was met.
Given the early closure of the study, no updated or additional efficacy analyses were performed after the interim analysis. A biomarker analysis was conducted in January 2014, based on the data from the cutoff date of 13 September 2013. The safety analysis was updated with a new cutoff date of 28 February 2014.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tivozanib + mFOLFOX6 | Experimental | Participants received 1.5 mg of tivozanib orally once daily beginning on Day 1 of each cycle for 21 days followed by 7 days off treatment. Participants also received modified FOLFOX6 (mFOLFOX6) chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
| Bevacizumab + mFOLFOX6 | Active Comparator | Participants received a dose of 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle. Participants also received mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tivozanib | Drug | Capsules for oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Investigator-assessed Progression-Free Survival (PFS) | The time from the date of randomization until objective tumor progression or death due to any cause. Objective tumor progression was determined through radiological imaging and based on the requirements of the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1): Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions. Participants who did not progress or had not died at the time of the analysis were censored at the date of last tumor assessment where non-progression was documented. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) Based on Independent Radiological Review (IRR) | The time from the date of randomization until the date of radiological disease progression assessed by the IRR or until death due to any cause, even in the absence of radiological progression. | 3 years |
| Overall Survival (OS) |
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Inclusion Criteria:
Exclusion Criteria:
Any prior Vascular Endothelial Growth Factor (VEGF)-directed therapy or any other agent or investigational agent targeting the VEGF pathway
Primary Central Nervous System (CNS) malignancies or CNS metastases
Hematologic abnormalities:
Serum chemistry abnormalities:
Significant cardiovascular disease
Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
Non-healing wound, bone fracture, or skin ulcer
Inadequate recovery from any prior surgical procedure or major surgical procedure within 8 weeks prior to administration, or anticipation of major surgical procedure during the course of the study
History of significant gastrointestinal (GI) toxicity, diarrhea, or stomatitis within the last 6 weeks
An active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
Serious/active infection or infection requiring antibiotics
Significant bleeding disorders within 6 months prior to administration of first dose of study drug
Active second primary malignancy, other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subject is not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for > 5 years
History of allergic reactions, or intolerance, attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, history of Grade 3 hypersensitivity to oxaliplatin, history of allergic reaction to folic acid
Female subject is pregnant or lactating
Known history of genetic or acquired immune suppression disease including Human Immunodeficiency Virus (HIV); subjects on immune suppressive therapy for organ transplant
Inability to swallow pills, malabsorption syndrome or gastrointestinal disease, major resection of the stomach or small bowel, or gastric bypass
Uncontrolled neuro-psychiatric disorder or altered mental status
Peripheral neuropathy ≥ Grade 2
Participating in another interventional protocol
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | AVEO Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Banner MD Anderson Cancer Research Center | Gilbert | Arizona | 85234 | United States | ||
| Genesis Cancer Center |
Participants were randomized in a 2:1 ratio (tivozanib to bevacizumab) and stratified by lactate dehydrogenase (LDH) status (< 1.5 x the upper limit of normal [ULN] or > 1.5 x ULN), origin of cancer (rectal or colon) and number of metastatic sites (1 or > 2).
Participants were at least 18 years of age with Stage IV metastatic colorectal cancer (mCRC) and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1).
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| ID | Title | Description |
|---|---|---|
| FG000 | Tivozanib + mFOLFOX6 | Participants received 1.5 mg tivozanib orally once daily beginning on Day 1 of each 28-day cycle for 21 days followed by 7 days off treatment. Participants also received modified FOLFOX6 (mFOLFOX6) chemotherapy consisting of oxaliplatin, 85 mg/m^2, leucovorin 400 mg/m^2, and 5-fluorouracil 400 mg/m^2 bolus then 2400 mg/m^2 every 2 weeks on Days 1 and 15 of each cycle. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Bevacizumab | Drug | Solution for intravenous infusion |
|
|
| mFOLFOX6 | Drug | mFOLFOX6 regimen is a combination therapy of oxaliplatin 85 mg/m^2 administered as an intravenous bolus over 2 hours on Days 1 and 15, leucovorin calcium 400 mg/m^2 administered as an intravenous bolus over 2 hours on Days 1 and 15, fluorouracil 400 mg/m^2 administered as an intravenous bolus over 5 to 15 minutes on Days 1 and 15, then 2400 mg/m^2 continuous intravenous infusion over 46 hours on Days 1 to 3 and 15 to 17. |
|
Overall survival (OS) is defined as the time from the date of randomization until the documented date of death. Participants still alive at the time of analysis were censored on the last day the participant was known to be alive. |
| From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Objective Response Rate (ORR) | Objective response rate is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) confirmed a minimum of four weeks apart based on RECIST 1.1 criteria. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and no progression of non-target lesions and no new lesions, or, disappearance of all target lesions and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Duration of Response (DoR) | Duration of response (DoR) is defined as the time from the date of the first documented response of CR or PR (whichever is first recorded) to documented progression or death. If a participant did not progress or had not died at the time of analysis, the duration of response was censored at the date of last tumor assessment. Duration of response is only defined for participants whose best overall response was CR or PR. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Time to Treatment Failure (TTF) | Time to Treatment Failure (TTF) is defined as the time from randomization to last dose date of tivozanib/bevacizumab. If a participant discontinued treatment for any reason, the participant was considered as an event. Participants remaining on treatment at the time of analysis were censored at date of last dose. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Health Related Quality of Life (HRQoL) | Time to deterioration in HRQoL measured by Colorectal cancer (CRC) subscale of the Functional Assessment of cancer Therapy Colorectal (FACT-C) scale, change in score from baseline using the European Quality of Life - 5 Dimensions (EQ-5D) and Fact Colorectal Symptom Index (FCSI) were not evaluated due to study closure. | 3 years |
| Safety as Assessed by Physical Examination, Vital Signs, Laboratory Assessments, 12-lead Electrocardiogram (ECGs), and Adverse Events (AEs) | An abnormality identified during a medical test is defined as an AE if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study medication or was clinically significant in the investigator's opinion. An AE was serious if it resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly or birth defect, required or prolonged inpatient hospitalization or other medically important event. AEs, including abnormal clinical laboratory values, were graded using the National Cancer Institute Common Terminology Criteria for Grading Adverse Events (NCI-CTCAE) Version 4.03 per the following: 1=mild; 2= moderate; 3= severe; 4= life threatening; 5=death. Treatment-related AEs were defined as events where the relationship to study drug was marked as probably or possibly, or was missing. | From first dose through 30 days after last dose of either tivozanib or bevacizumab, until the data cut-off date of 28 February 2014. The median duration of treatment was 168.0 days in the tivozanib (tiv) arm and 162.0 days in the bevacizumab (bev) arm. |
| Progression-free Survival Events by Lactate Dehydrogenase (LDH) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum lactate dehydrogenase status. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-A (VEGF-A) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum vascular endothelial growth factor-A (VEGF-A) level. VEGF-A protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-C (VEGF-C) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum VEGF-C level. VEGF-C protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-free Survival Events by Serum VEGF-C / VEGF-A Ratio | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum VEGF-C/VEGF-A ratio. VEGF-A and VEGF-C protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the ratio is expressed relative to the observed median. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-2 (sVEGFR-2) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum sVEGFR-2 level. sVEGFR-2 protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-3 (sVEGFR-3) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum sVEGFR-3 level. sVEGFR-3 protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Serum Interleukin-8 (IL-8) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum interleukin-8 level. IL-8 protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Serum Neuropilin Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum neuropilin level. Neuropilin protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Tumor VEGF-A Ribonucleic Acid (RNA) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-A RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Tumor VEGF-C RNA Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-C RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Tumor VEGF-C / VEGF-A RNA Ratio | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-C/VEGF-A RNA ratio. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Tumor VEGF-D RNA Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-D RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Progression-Free Survival Events by Tumor Placental Growth Factor (PIGF) RNA Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor PIGF RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| Hot Springs |
| Arizona |
| 71913 |
| United States |
| Arizona Clinical Research Center | Tucson | Arizona | 85715 | United States |
| University of California San Diego-Morris Cancer Center | La Jolla | California | 92093 | United States |
| UC Irvine Medical Center, Division of Hematology/Oncology | Orange | California | 92868 | United States |
| Desert Hematology Oncology Medical Group, Inc. | Rancho Mirage | California | 92270 | United States |
| Mountain Blue Cancer Care Center | Golden | Colorado | 80033 | United States |
| University of Florida, Davis Cancer Center (VA) | Gainesville | Florida | 32610 | United States |
| Cleveland Clinic Florida | Weston | Florida | 33331 | United States |
| Queen's Medical Center | Honolulu | Hawaii | 96813 | United States |
| University of Hawaii | Honolulu | Hawaii | 96813 | United States |
| Kaiser Foundation Hospitals | Honolulu | Hawaii | 96819 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Illinios Cancer Care | Peoria | Illinois | 61615 | United States |
| Investigative Clinical Research of Indiana, LLC | Indianapolis | Indiana | 46260 | United States |
| Horizon Oncology Research, Inc. | Lafayette | Indiana | 47905 | United States |
| Associates of Oncology Hematology, P.C. | Rockville | Maryland | 20850 | United States |
| University of Michigan Health | Ann Arbor | Michigan | 48109 | United States |
| NYU Cancer Institute | New York | New York | 10016 | United States |
| Alamance Regional Medical Center | Burlington | North Carolina | 27215 | United States |
| Tri Country Hematology / Oncology | Canton | Ohio | 44718 | United States |
| Signal Point Clinical Research Center, LLC | Middletown | Ohio | 45042 | United States |
| Cancer Care Associates | Tulsa | Oklahoma | 74136 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Oncology Hematology of Lehigh Valley | Bethlehem | Pennsylvania | 18015 | United States |
| Northern Utah Associates | Ogden | Utah | 84403 | United States |
| Seattle Cancer Care Alliance | Seattle | Washington | 98109 | United States |
| St George Hospital | Kogarah | New South Wales | 2217 | Australia |
| Tweed Hospital | Tweed Heads | New South Wales | 2485 | Australia |
| Calvary Mater Newcastle | Waratah | New South Wales | 2298 | Australia |
| Flinders Medical Centre | Bedford Park | South Australia | 5042 | Australia |
| Royal Hobart Hospital | Hobart | Tasmania | 7000 | Australia |
| Ballarat Health Services | Ballarat | Victoria | 3350 | Australia |
| Cabrini Hospital Malvern | Malvern | Victoria | 3144 | Australia |
| Border Medical Oncology | Wodonga | Victoria | 3690 | Australia |
| Medizinische Universitat Graz | Graz | 8036 | Austria |
| Salzburger Landesklinken | Salzburg | 5020 | Austria |
| Klinikum Wels-Grieskirchen GmbH | Wels | 4600 | Austria |
| Ziekenhuisnetwerk Antwerpen - AZ Middelheim | Antwerp | 2020 | Belgium |
| Imelda VZW | Bonheiden | 2820 | Belgium |
| AZ Sint-Lucas Brugge | Bruges | 8310 | Belgium |
| AZ Groeninge - Campus Sint-Niklaas | Kortrijk | 8500 | Belgium |
| British Columbia Cancer Agency | Vancouver | British Columbia | V5Z 4E6 | Canada |
| QEII Health Science Centre | Halifax | Nova Scotia | B3H 2Y9 | Canada |
| Hopital De La Cite-De-La-Sante | Laval | Quebec | H7M 3L9 | Canada |
| Hopital Saint-Luc - Pavillon Principal | Montreal | Quebec | H2X 3J4 | Canada |
| Chuq Centre Hospitalier Universitaire De Quebec | Québec | Quebec | G1R 2J6 | Canada |
| Masarykuv onkologicky ustav | Brno | 656 53 | Czechia |
| Fakultni nemocnice Hradec Kralove | Hradec Králové | 500 05 | Czechia |
| Tampereen yliopistollinen sairaala | Tampere | FI-33520 | Finland |
| Turun yliopistollinen keskussairaala | Turku | FI-20520 | Finland |
| Orszagos Onkologiai Intezet | Budapest | 1122 | Hungary |
| Petz Aladar Megyei Oktato Korhaz | Győr | 9024 | Hungary |
| Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza | Gyula | 5700 | Hungary |
| Fejer Megyei Szent Gyorgy Korhaz | Székesfehérvár | 8000 | Hungary |
| Azienda Ospedaliero- Universitaria di Bologna - Policlinico S.Orsola-Malpighi | Bologna | 40128 | Italy |
| Fondazione del Piemonte per I'Oncologia IRCC | Candiolo | 10060 | Italy |
| IRCCS Azienda Ospedaliera Universitaria San Martino - Istituto Nazionale per la Ricerca sul Cancro | Genova | 16132 | Italy |
| Istituto Clinico Humanitas | Rozzano (MI) | 20089 | Italy |
| Amphia Ziekenhuis | Breda | 4819 EV | Netherlands |
| Hospital Universitario Miguel Servet | Zaragoza | Aragon | 50009 | Spain |
| Hospital Universitario Marques de Valdecilla | Santander | Cantabria | 39008 | Spain |
| Corporacio Sanitaria Parc Tauli | Sabadell | Catalonia | 08208 | Spain |
| Hospital Mutua de Terrassa | Terrassa | Catalonia | 08221 | Spain |
| Centro Oncologico de Galicia | Galicia | 15009 | Spain |
| Centro Integral Oncologico Clara Campal | Madrid | 28050 | Spain |
| Addenbrooke's Hospital | Cambridge | CB2 2QQ | United Kingdom |
| Western General Hospital | Edinburgh | EH4 2XU | United Kingdom |
| Beatson West of Scotland Cancer Center | Glasgow | G12 0YN | United Kingdom |
| University College Hospital | London | NW1 2BU | United Kingdom |
| Maidstone Hospital | Maidstone | ME16 9QQ | United Kingdom |
| Christie Hospital | Manchester | M20 4BX | United Kingdom |
| Peterborough and Stamford Hospitals NHS Foundation Trust | Peterborough | PE3 6DA | United Kingdom |
| FG001 | Bevacizumab + mFOLFOX6 | Participants received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle. Participants also received mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Tivozanib + mFOLFOX6 | Participants received 1.5 mg tivozanib orally once daily beginning on Day 1 of each cycle for 21 days followed by 7 days off treatment. Participants also received mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| BG001 | Bevacizumab + mFOLFOX6 | Participants received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle. Participants also received mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Eastern Cooperative Oncology Group (ECOG) performance status | ECOG criteria: 0: Fully active. 1: Ambulatory, carry out work of a light or sedentary nature. 2: Ambulatory, capable of all self-care. 3: Capable of limited self-care, confined to bed or chair more than 50% of waking hours. 4: Completely disabled, no self-care, totally confined to bed or chair. 5: Dead. | Number | participants |
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| Lactate dehydrogenase (LDH) Status | The upper limit of normal (ULN) from the site was used. | Number | participants |
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| Origin of Cancer | Number | participants |
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| Number of metastatic sites/organs | Number | participants |
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| Kirsten rat sarcoma (KRAS) Mutation Status | Number | participants |
| ||||||||||||||||
| Time Since Initial Diagnosis | Mean | Standard Deviation | months |
| |||||||||||||||
| Number of metastatic sites at screening | Mean | Standard Deviation | metastatic sites |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Investigator-assessed Progression-Free Survival (PFS) | The time from the date of randomization until objective tumor progression or death due to any cause. Objective tumor progression was determined through radiological imaging and based on the requirements of the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1): Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions. Participants who did not progress or had not died at the time of the analysis were censored at the date of last tumor assessment where non-progression was documented. | The full analysis set included all randomized participants. | Posted | Median | 95% Confidence Interval | months | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
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| Secondary | Progression-Free Survival (PFS) Based on Independent Radiological Review (IRR) | The time from the date of randomization until the date of radiological disease progression assessed by the IRR or until death due to any cause, even in the absence of radiological progression. | Analysis was not performed due to study closure. | Posted | 3 years |
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| Secondary | Overall Survival (OS) | Overall survival (OS) is defined as the time from the date of randomization until the documented date of death. Participants still alive at the time of analysis were censored on the last day the participant was known to be alive. | Full analysis set | Posted | Median | 95% Confidence Interval | months | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
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| Secondary | Objective Response Rate (ORR) | Objective response rate is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) confirmed a minimum of four weeks apart based on RECIST 1.1 criteria. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and no progression of non-target lesions and no new lesions, or, disappearance of all target lesions and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions. | Full analysis set | Posted | Number | percentage of participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response (DoR) | Duration of response (DoR) is defined as the time from the date of the first documented response of CR or PR (whichever is first recorded) to documented progression or death. If a participant did not progress or had not died at the time of analysis, the duration of response was censored at the date of last tumor assessment. Duration of response is only defined for participants whose best overall response was CR or PR. | Participants with a best overall response of complete response (CR) or partial response (PR). | Posted | Median | 95% Confidence Interval | months | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Treatment Failure (TTF) | Time to Treatment Failure (TTF) is defined as the time from randomization to last dose date of tivozanib/bevacizumab. If a participant discontinued treatment for any reason, the participant was considered as an event. Participants remaining on treatment at the time of analysis were censored at date of last dose. | Full analysis set | Posted | Median | 95% Confidence Interval | months | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Health Related Quality of Life (HRQoL) | Time to deterioration in HRQoL measured by Colorectal cancer (CRC) subscale of the Functional Assessment of cancer Therapy Colorectal (FACT-C) scale, change in score from baseline using the European Quality of Life - 5 Dimensions (EQ-5D) and Fact Colorectal Symptom Index (FCSI) were not evaluated due to study closure. | Analysis was not performed due to study closure. | Posted | 3 years |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Safety as Assessed by Physical Examination, Vital Signs, Laboratory Assessments, 12-lead Electrocardiogram (ECGs), and Adverse Events (AEs) | An abnormality identified during a medical test is defined as an AE if the abnormality induced clinical signs or symptoms, required active intervention, interruption or discontinuation of study medication or was clinically significant in the investigator's opinion. An AE was serious if it resulted in death, was life-threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly or birth defect, required or prolonged inpatient hospitalization or other medically important event. AEs, including abnormal clinical laboratory values, were graded using the National Cancer Institute Common Terminology Criteria for Grading Adverse Events (NCI-CTCAE) Version 4.03 per the following: 1=mild; 2= moderate; 3= severe; 4= life threatening; 5=death. Treatment-related AEs were defined as events where the relationship to study drug was marked as probably or possibly, or was missing. | The safety analysis set consisted of all randomized participants who received at least one dose of study drug (tivozanib or bevacizumab), analyzed according to the treatment actually received. | Posted | Number | participants | From first dose through 30 days after last dose of either tivozanib or bevacizumab, until the data cut-off date of 28 February 2014. The median duration of treatment was 168.0 days in the tivozanib (tiv) arm and 162.0 days in the bevacizumab (bev) arm. |
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| Secondary | Progression-free Survival Events by Lactate Dehydrogenase (LDH) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum lactate dehydrogenase status. | Full analysis set | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-A (VEGF-A) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum vascular endothelial growth factor-A (VEGF-A) level. VEGF-A protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | Full analysis set with available serum protein samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival Events by Serum Vascular Endothelial Growth Factor-C (VEGF-C) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum VEGF-C level. VEGF-C protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | Full analysis set with available serum protein samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival Events by Serum VEGF-C / VEGF-A Ratio | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum VEGF-C/VEGF-A ratio. VEGF-A and VEGF-C protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the ratio is expressed relative to the observed median. | Full analysis set with available serum protein samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-2 (sVEGFR-2) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum sVEGFR-2 level. sVEGFR-2 protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | Full analysis set with available serum protein samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Soluble Vascular Endothelial Growth Factor Receptor-3 (sVEGFR-3) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum sVEGFR-3 level. sVEGFR-3 protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | Full analysis set with available serum protein samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Serum Interleukin-8 (IL-8) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum interleukin-8 level. IL-8 protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | Full analysis set with available serum protein samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Serum Neuropilin Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline serum neuropilin level. Neuropilin protein levels were quantified using enzyme-liked immunosorbent assay (ELISA); the level of protein is expressed relative to the observed median level. | Full analysis set with available serum protein samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Tumor VEGF-A Ribonucleic Acid (RNA) Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-A RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | Full analysis set with available tumor biopsy RNA samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Tumor VEGF-C RNA Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-C RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | Full analysis set with available tumor biopsy RNA samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Tumor VEGF-C / VEGF-A RNA Ratio | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-C/VEGF-A RNA ratio. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | Full analysis set with available tumor biopsy RNA samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Tumor VEGF-D RNA Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor VEGF-D RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | Full analysis set with available tumor biopsy RNA samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-Free Survival Events by Tumor Placental Growth Factor (PIGF) RNA Level | The number of participants with a progression-free survival event (radiological progression assessed by the investigator or death due to any cause) reported by Baseline tumor PIGF RNA level. RNA was purified from biopsy tissue and measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Since low cycle threshold (CT) values reflect high RNA expression, the inverse of CT values were used to derive tumor categories. RNA level is expressed relative to the observed median level. | Full analysis set with available tumor biopsy RNA samples | Posted | Number | participants | From randomization until the analysis cut-off date of 13 September 2013; median time on study drug was 167 days in the tivozanib group and 162 days in the bevacizumab group. |
|
From the first dose through 30 days after last dose of either tivozanib or bevacizumab, until the data cut-off date of 28 February 2014. The median duration of treatment was 168.0 days in the tivozanib arm and 162.0 days in the bevacizumab arm.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tivozanib + mFOLFOX6 | Participants received 1.5 mg of tivozanib orally once daily beginning on Day 1 of each cycle for 21 days followed by 7 days off treatment. Participants also received mFOLFOX6) chemotherapy every 2 weeks on Days 1 and 15 of each cycle. | 82 | 177 | 175 | 177 | ||
| EG001 | Bevacizumab + mFOLFOX6 | Participants received a dose of 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle. Participants also received mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. | 42 | 87 | 85 | 87 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Anal ulcer | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Colonic obstruction | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Peritonitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pneumatosis intestinalis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Parotitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Perihepatic abscess | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Peritonitis bacterial | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Subcutaneous abscess | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Enterocolitis viral | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Catheter site erythema | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Device malfunction | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Stent malfunction | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypertensive emergency | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Subclavian vein thrombosis | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Venous thrombosis | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Agranulocytosis | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Thrombotic thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Aortic valve disease | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cardiopulmonary failure | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Intracardiac thrombus | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Reversible posterior leukoencephalopathy syndrome | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Monoparesis | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Heart rate increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Troponin increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hepatic haemorrhage | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Intervertebral disc degeneration | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Mobility decreased | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Angiomyolipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Systematic Assessment |
| |
| Duodenal neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
| |
| Wound necrosis | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Anorectal operation | Surgical and medical procedures | MedDRA 13.1 | Systematic Assessment |
| |
| Chemotherapy | Surgical and medical procedures | MedDRA 13.1 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Vaginal fistula | Reproductive system and breast disorders | MedDRA 13.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Temperature intolerance | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Infusion related reaction | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA 13.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 13.1 | Systematic Assessment |
|
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or after 18 months after database lock, whichever comes first. Sponsor must receive a site's manuscript at least 30 days prior to publication for review and comment. Sponsor may delay the publication for up to 60 days to seek patent protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | AVEO | 1.617.588.1960 | clinical@aveooncology.com |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C553176 | tivozanib |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Black or African American |
|
| Asian |
|
| Native Hawaiian or other Pacific Islander |
|
| Other |
|
| Hungary |
|
| Czech Republic |
|
| Canada |
|
| Finland |
|
| Spain |
|
| Belgium |
|
| Austria |
|
| Australia |
|
| Netherlands |
|
| United Kingdom |
|
| Italy |
|
| ECOG Performance Status 1 |
|
| ECOG Performance Status 2 |
|
| ECOG Performance Status 3 |
|
| ECOG Performance Status 4 |
|
| ≥ 1.5 Upper Limit of Normal |
|
| Colon |
|
| 2 |
|
| 3 |
|
| ≥ 4 |
|
| Mutant |
|
| Unknown |
|
| No |
| Superiority or Other |
|
|
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
|
|
| OG001 | Bevacizumab + mFOLFOX6 | Participants received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
| OG003 | Bevacizumab : LDH ≥ 1.5 ULN | Participants with LDH status ≥ 1.5 ULN received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| OG002 |
| Bevacizumab: VEGF-A < Median |
Participants with VEGF-A levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: VEGF-A ≥ Median | Participants with VEGF-A levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| Bevacizumab: VEGF-C < Median |
Participants with VEGF-C levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: VEGF-C ≥ Median | Participants with VEGF-C levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| Bevacizumab: VEGF-C/VEGF-A < Median |
Participants with VEGF-C/VEGF-A ratio < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: VEGF-C/VEGF-A ≥ Median | Participants with VEGF-C/VEGF-A ratio ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| Bevacizumab: sVEGFR-2 < Median |
Participants with sVEGFR-2 levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: sVEGFR-2 ≥ Median | Participants with sVEGFR-2 levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| Bevacizumab: sVEGFR-3 < Median |
Participants with sVEGFR-3 levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: sVEGFR-3 ≥ Median | Participants with sVEGFR-3 levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
Participants with IL-8 levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: IL-8 ≥ Median | Participants with IL-8 levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| Bevacizumab: Neuropilin < Median |
Participants with neuropilin levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and FOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: Neuropilin ≥ Median | Participants with neuropilin levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| OG002 | Bevacizumab: VEGF-A RNA < Median | Participants with VEGF-A RNA levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: VEGF-A RNA ≥ Median | Participants with VEGF-A RNA levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| OG002 | Bevacizumab: VEGF-C RNA < Median | Participants with VEGF-C RNA levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: VEGF-A RNA ≥ Median | Participants with VEGF-C RNA levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| OG002 | Bevacizumab: VEGF-C/VEGF-A RNA < Median | Participants with VEGF-C/VEGF-A RNA ratio < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: VEGF-C/VEGF-A RNA ≥ Median | Participants with VEGF-C/VEGF-A RNA ratio ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| OG002 | Bevacizumab: VEGF-D RNA < Median | Participants with VEGF-D RNA levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: VEGF-D RNA ≥ Median | Participants with VEGF-D RNA levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|
| OG002 | Bevacizumab: PIGF RNA < Median | Participants with PIGF RNA levels < median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
| OG003 | Bevacizumab: PIGF RNA ≥ Median | Participants with PIGF RNA levels ≥ median received 5 mg/kg bevacizumab via intravenous infusion every 2 weeks on Days 1 and 15 of each cycle and mFOLFOX6 chemotherapy every 2 weeks on Days 1 and 15 of each cycle. |
|
|
|