Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This open-label, single arm, multicenter study evaluated the resection rate in participants with colorectal cancer and previously untreated unresectable liver-only metastases after adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting. Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and postoperatively, unless they experienced progressive disease or unacceptable toxicity.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bevacizumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-FU based doublet chemotherapy | Drug | Standard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving Complete Resection (R0 Resection) | R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported. | At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection) | R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Beijing | 100142 | China | |||
| Sun Yet-sen University Cancer Center |
Protocol did not specify any particular 5-Flurouracil (5-FU) based doublet chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Bevacizumab | Participants received standard 5-Flurouracil (5-FU) based chemotherapy plus bevacizumab 5 milligrams per kilograms (mg/kg) intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| bevacizumab | Drug | 5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively |
|
|
| At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks) |
| Percentage of Participants Achieving Objective Response | Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
| Number of Participants With Disease Progression or Relapse or Death | According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
| Progression Free Survival (PFS) | Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS. | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
| Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18 | Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis. | Months 3, 6, 9, 12, 15, and 18 |
| Number of Participants With Disease Relapse or Death | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
| Disease Free Survival (DFS) | Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab. | Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years) |
| Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12 | Months 3, 6, 9, and 12 |
| Guangzhou |
| 510060 |
| China |
| The Second Affiliated Hospital of Zhejiang University College | Hangzhou | 310009 | China |
| The 2nd Affiliated Hospital of Harbin Medical University | Harbin | 150001 | China |
| Zhongshan Hospital Fudan University | Shanghai | 200032 | China |
| Liaoning cancer Hospital & Institute | Shenyang | 110042 | China |
| Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology | Wuhan | 430022 | China |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Intent-to-treat (ITT) population included all participants enrolled in the study.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Bevacizumab | Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 | Percentage of Participants Achieving Complete Resection (R0 Resection) | R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported. | ITT population | Posted | Number | 95% Confidence Interval | percentage of participants | At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks) |
|
|
| |||||||||||||||||||||||||
| Secondary | Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection) | R1 resection was defined as achievement of incomplete tumor resection with microscopic involvement of a margin after pre-operative chemotherapy plus bevacizumab, as confirmed by pathology. Participants with R1 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported. | ITT population | Posted | Number | 95% Confidence Interval | percentage of participants | At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks) |
|
| ||||||||||||||||||||||||||
| Secondary | Percentage of Participants Achieving Objective Response | Objective response rate was defined as the percentage of participants who achieved either Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1. This is defined as the best response recorded from the start of trial treatment until disease progression (or death). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [≥] 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. | ITT population | Posted | Number | 95% Confidence Interval | percentage of participants | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
|
| ||||||||||||||||||||||||||
| Secondary | Number of Participants With Disease Progression or Relapse or Death | According to RECIST v1.1 Progressive Disease is defined as a 20 % or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. | ITT population | Posted | Number | participants | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
|
| |||||||||||||||||||||||||||
| Secondary | Progression Free Survival (PFS) | Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. Kaplan-Meier curves were used to display PFS. | ITT population | Posted | Median | 95% Confidence Interval | months | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
|
| ||||||||||||||||||||||||||
| Secondary | Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18 | Progressive Disease is defined as a 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions) taking as reference the smallest lesion diameter recorded since the treatment started or appearance of one or more new non-target lesions. PFS was defined as the time from initiation of study treatment to disease progression, as determined by the investigator using RECIST v1.1 criterion, or relapse after resection of liver metastases or death from any cause. The probability was estimated by Kaplan Meier curve analysis. | ITT population; Number of participants analyzed equals (=) number of participants who had surgery. | Posted | Number | 95% Confidence Interval | PP of being alive and progression free | Months 3, 6, 9, 12, 15, and 18 |
|
| ||||||||||||||||||||||||||
| Secondary | Number of Participants With Disease Relapse or Death | ITT population | Posted | Number | participants | Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall) |
|
| ||||||||||||||||||||||||||||
| Secondary | Disease Free Survival (DFS) | Disease Free Survival (DFS) was defined as the time from complete resection of liver metastases to disease relapse or death, for participants who achieve complete resection after pre-operative treatment with standard 5-FU based doublet regimen plus bevacizumab. | ITT population; Here, number of participants analyzed = participants who underwent study specified surgery. Participants who underwent surgery but did not achieve complete resection were censored. | Posted | Median | 95% Confidence Interval | months | Complete resection date up to disease relapse or death until data cutoff on 12 May 2016 (up to approximately 3.5 years) |
|
| ||||||||||||||||||||||||||
| Secondary | Percent Probability Of Being Alive and Disease Free at Months 3, 6, 9, and 12 | ITT population | Posted | Median | 95% Confidence Interval | PP of being alive and disease free | Months 3, 6, 9, and 12 |
|
|
Adverse events were recorded from the date of Screening until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)
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 | Bevacizumab | Participants received standard 5-FU based chemotherapy plus bevacizumab 5 mg/kg intravenous infusion every two week cycle for a maximum of 12 cycles unless they experienced progressive disease, unacceptable toxicities or participant refusal. | 4 | 50 | 26 | 50 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Scrotal infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 1-800-821-8590 | genentech@druginfo.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 |
|---|---|
| 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
|
| Counts |
|---|
| Participants |
|
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| 3 Months |
| |||||
| 6 Months |
| |||||
| 9 Months |
| |||||
| 12 Months |
|