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| ID | Type | Description | Link |
|---|---|---|---|
| 2007_529 | Other Identifier | Telerex Number |
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This study will compare the safety and efficacy of dalotuzumab (MK-0646) in combination with cetuximab and irinotecan in treating participants with wild type KRAS (wtKRAS) metastatic colorectal cancer (CRC) compared to cetuximab and irinotecan alone.
The primary study hypothesis is that administration of dalotuzumab in combination with cetuximab and irinotecan to participants with metastatic CRC expressing the wtKRAS genotype improves Overall Survival OR Progression-free Survival compared to participants treated with cetuximab and irinotecan alone.
Dalotuzumab is a humanized monoclonal antibody (mAb) that targets the insulin-like growth factor type 1 receptor-1 (IGF-1R). Dalotuzumab may act through inhibition of insulin-like growth factor-1 (IGF-1)-mediated cell signaling to cause reductions in tumor growth and spread antibody dependent cell-mediated cytotoxicity.
In preclinical studies, dalotuzumab improved the activity of an anti-epidermal growth factor receptor (EGFR) mAb and the activity of erlotinib, a small molecule inhibitor of EGFR.
All eligible participants will receive cetuximab 400 mg/m^2 infusion over 120 minutes followed by weekly infusions of cetuximab 250 mg/m^2 over 60-120 minutes along with irinotecan infusion over 30-90 minutes. Dosage of irinotecan will be the same as most recent pre-study therapy. Participants will then be assigned to one of three treatment double-blind arms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dalotuzumab 10 mg/kg Q1W (DB) | Experimental | In double-blind (DB) Week 1, participants receive cetuximab 400 mg/m^2 intravenously (IV) loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants receive cetuximab 250 mg/m^2 IV one time each week (Q1W) maintenance dose, irinotecan IV Q1W and DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
|
| Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL) | Experimental | In the open-label (OL) portion of the study, ≥6 participants receive cetuximab 400 mg/m^2 Q1W + irinotecan Q1W at their pre-study dosage + OL dalotuzumab (loading dose of 15 mg/kg IV followed by a maintenance dose of 7.5 mg/kg 2 weeks later) to verify the safety of the regimen. In DB Week 1, participants receive cetuximab 400 mg/m^2 IV + irinotecan IV. In DB Week 2, participants receive cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants receive cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants receive cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. |
|
| Dalotuzumab 10 mg/kg Q1W (OL) | Experimental | In the OL portion of the study, ≥6 participants receive cetuximab 400 mg/m^2 Q1W+ irinotecan Q1W at their pre-study dosage + OL dalotuzumab 10 mg/kg IV Q1W to verify the safety of the regimen. In DB Week 1, participants receive cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants receive cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dalotuzumab | Biological | IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | The OS of participants with metastatic colorectal cancer (CRC) expressing the KRAS wild-type (wtKRAS) tumor genotype (indicating no detection of KRAS mutation) was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and is reported in months. | Up to 12 weeks after last dose of study drug (Up to 35 months) |
| Progression-free Survival (PFS) | The PFS of participants with metastatic CRC expressing the wtKRAS genotype was defined as the time from the first day of study treatment to the first documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST 1.0) as documented by an independent core laboratory, or death due to any cause, whichever occurred first. Disease progression was defined as either a 20% or greater relative increase in the sum of diameters of target lesions OR an absolute increase of at least 5mm in the sum of lesions or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. | Up to last dose of study drug (Up to 32 months) |
| Percentage of Participants Who Have a Clinical or Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 to 5 Toxicity | An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. (Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4=Life-threatening consequences; urgent intervention indicated. Grade 5=Death related to AE.) Participants were monitored for AEs until the earlier of study discontinuation or 30 days after dalotuzumab/placebo discontinuation. AE grades were assessed using the National Cancer Institute (NCI) CTCAE, version 3.0. | Up to 30 days after last dose of study drug (Up to 33 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) of Dalotuzumab in Combination With Cetuximab + Irinotecan Versus ORR of Cetuximab + Irinotecan Alone in Participants With Wild Type of Colorectal Cancer | ORR, using RECIST 1.0, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on central radiology review. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26405092 | Background | Sclafani F, Kim TY, Cunningham D, Kim TW, Tabernero J, Schmoll HJ, Roh JK, Kim SY, Park YS, Guren TK, Hawkes E, Clarke SJ, Ferry D, Frodin JE, Ayers M, Nebozhyn M, Peckitt C, Loboda A, Mauro DJ, Watkins DJ. A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory, KRAS Wild-Type, Metastatic Colorectal Cancer. J Natl Cancer Inst. 2015 Sep 23;107(12):djv258. doi: 10.1093/jnci/djv258. Print 2015 Dec. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dalotuzumab 10 mg/kg Q1W (DB) | In double-blind (DB) Week 1, participants received cetuximab 400 mg/m^2 intravenously (IV) loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV one time each week (Q1W) maintenance dose, irinotecan IV Q1W and DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
| FG001 | Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL) | In the open-label (OL) portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W + irinotecan Q1W at their pre-study dosage + OL dalotuzumab (loading dose of 15 mg/kg IV followed by a maintenance dose of 7.5 mg/kg 2 weeks later) to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV one time every two weeks (Q2W) for up to 32 months of treatment. |
| FG002 | Dalotuzumab 10 mg/kg Q1W (OL) | In the OL portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W+ irinotecan Q1W at their pre-study dosage + OL dalotuzumab 10 mg/kg IV Q1W to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
| FG003 | Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. |
| FG004 | Placebo + Cetuximab + Irinotecan (DB) | In DB Week 1, participants received a cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Baseline Analysis Population was the All Participants As Treated (APAT) population and consisted of all participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dalotuzumab 10 mg/kg Q1W (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W maintenance dose, irinotecan IV Q1W and DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Overall Survival (OS) | The OS of participants with metastatic colorectal cancer (CRC) expressing the KRAS wild-type (wtKRAS) tumor genotype (indicating no detection of KRAS mutation) was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and is reported in months. | The Intent-to-Treat (ITT) population consisted of all participants who had a wtKRAS tumor genotype. The efficacy analyses were planned for and only included participants from the DB portion of the study. Participants from the OL portion were excluded from the analyses. Participants were counted in the group to which they were randomized. | Posted | Median | Full Range | Months | Up to 12 weeks after last dose of study drug (Up to 35 months) |
|
Up to 30 days after last dose of study drug (Up to 33 months)
The APaT population consisted of all randomized participants who received ≥1 dose of study drug. Participants were included in the treatment group corresponding to the study drug they actually received.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dalotuzumab 10 mg/kg Q1W (BD) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W maintenance dose, irinotecan IV Q1W and DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C569480 | dalotuzumab |
| D000077146 | Irinotecan |
| D000068818 | Cetuximab |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
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|
| Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB) | Experimental | In DB Week 1, participants receive cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. In DB Week 2, participants receive cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants receive cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants receive cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. |
|
| Placebo + Cetuximab + Irinotecan (DB) | Active Comparator | In DB Week 1, participants receive cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants receive cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment. |
|
|
| irinotecan hydrochloride | Drug | IV infusion |
|
|
| cetuximab | Biological | IV infusion |
|
|
| placebo | Drug | IV infusion |
|
|
| Percentage of Participants Who Have a Drug-related Clinical or Laboratory CTCAE Grade 3 to 5 Toxicity | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. (Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4=Life-threatening consequences; urgent intervention indicated. Grade 5=Death related to AE.) Drug-related AEs were those AEs that were possibly, probably, or definitely related to study drug or protocol-specified procedures. Participants were monitored for AEs related to dalotuzumab or placebo until the earlier of study discontinuation or 30 days after dalotuzumab/placebo discontinuation. AE grades were assessed using the NCI CTCAE, version 3.0. | Up to 30 days after last dose of study drug (Up to 33 months) |
| Percentage of Participants Who Discontinue Study Drug Due to an AE | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. The percentage of participants who discontinued study drug due to an AE is presented. | Up to last dose of study drug (Up to 32 months) |
| Percentage of Participants Who Experience an AE of Infusion Site Reaction | The percentage of participants who experienced an AE of infusion site reaction is presented. | Up to 30 days after last dose of study drug (Up to 33 months) |
| Every 6 weeks (Up to 32 months) |
| Lost to Follow-up |
|
| Physician Decision |
|
| Progressive Disease |
|
| Protocol Violation |
|
| Terminated by Sponsor |
|
| Withdrawal by Subject |
|
| Other |
|
| Not Treated |
|
| Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL) |
In the OL portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W + irinotecan Q1W at their pre-study dosage + OL dalotuzumab (loading dose of 15 mg/kg IV followed by a maintenance dose of 7.5 mg/kg 2 weeks later) to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. |
| BG002 | Dalotuzumab 10 mg/kg Q1W (OL) | In the OL portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W+ irinotecan Q1W at their pre-study dosage + OL dalotuzumab 10 mg/kg IV Q1W to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
| BG003 | Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. |
| BG004 | Placebo + Cetuximab + Irinotecan (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment. |
| BG005 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
In DB Week 1, participants received cetuximab 400 mg/m^2 IV loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W maintenance dose, irinotecan IV Q1W and DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment.
| OG001 | Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL) | In the OL portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W + irinotecan Q1W at their pre-study dosage + OL dalotuzumab (loading dose of 15 mg/kg IV followed by a maintenance dose of 7.5 mg/kg 2 weeks later) to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. |
| OG002 | Dalotuzumab 10 mg/kg Q1W (OL) | In the OL portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W+ irinotecan Q1W at their pre-study dosage + OL dalotuzumab 10 mg/kg IV Q1W to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. |
| OG003 | Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. |
| OG004 | Placebo + Cetuximab + Irinotecan (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment. |
|
|
|
| Primary | Progression-free Survival (PFS) | The PFS of participants with metastatic CRC expressing the wtKRAS genotype was defined as the time from the first day of study treatment to the first documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST 1.0) as documented by an independent core laboratory, or death due to any cause, whichever occurred first. Disease progression was defined as either a 20% or greater relative increase in the sum of diameters of target lesions OR an absolute increase of at least 5mm in the sum of lesions or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. | The ITT population consisted of all participants who had a wtKRAS tumor genotype. The efficacy analyses were planned for and only included participants from the DB portion of the study. Participants from the OL portion were excluded from the analyses. Participants were counted in the group to which they were randomized. | Posted | Median | Full Range | Months | Up to last dose of study drug (Up to 32 months) |
|
|
|
|
| Primary | Percentage of Participants Who Have a Clinical or Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 to 5 Toxicity | An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. (Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4=Life-threatening consequences; urgent intervention indicated. Grade 5=Death related to AE.) Participants were monitored for AEs until the earlier of study discontinuation or 30 days after dalotuzumab/placebo discontinuation. AE grades were assessed using the National Cancer Institute (NCI) CTCAE, version 3.0. | The All Participants as Treated (APaT) population consisted of all randomized participants who received ≥1 dose of study drug. Participants were included in the treatment group corresponding to the study drug they actually received. | Posted | Number | Percentage of Participants | Up to 30 days after last dose of study drug (Up to 33 months) |
|
|
|
| Primary | Percentage of Participants Who Have a Drug-related Clinical or Laboratory CTCAE Grade 3 to 5 Toxicity | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. (Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4=Life-threatening consequences; urgent intervention indicated. Grade 5=Death related to AE.) Drug-related AEs were those AEs that were possibly, probably, or definitely related to study drug or protocol-specified procedures. Participants were monitored for AEs related to dalotuzumab or placebo until the earlier of study discontinuation or 30 days after dalotuzumab/placebo discontinuation. AE grades were assessed using the NCI CTCAE, version 3.0. | The APaT population consisted of all randomized participants who received ≥1 dose of study drug. Participants were included in the treatment group corresponding to the study drug they actually received. | Posted | Number | Percentage of Participants | Up to 30 days after last dose of study drug (Up to 33 months) |
|
|
|
| Primary | Percentage of Participants Who Discontinue Study Drug Due to an AE | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. The percentage of participants who discontinued study drug due to an AE is presented. | The APaT population consisted of all randomized participants who received ≥1 dose of study drug. Participants were included in the treatment group corresponding to the study drug they actually received. | Posted | Number | Percentage of Participants | Up to last dose of study drug (Up to 32 months) |
|
|
|
| Primary | Percentage of Participants Who Experience an AE of Infusion Site Reaction | The percentage of participants who experienced an AE of infusion site reaction is presented. | The APaT population consisted of all randomized participants who received ≥1 dose of study drug. Participants were included in the treatment group corresponding to the study drug they actually received. | Posted | Number | Percentage of Participants | Up to 30 days after last dose of study drug (Up to 33 months) |
|
|
|
| Secondary | Overall Response Rate (ORR) of Dalotuzumab in Combination With Cetuximab + Irinotecan Versus ORR of Cetuximab + Irinotecan Alone in Participants With Wild Type of Colorectal Cancer | ORR, using RECIST 1.0, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on central radiology review. | The ITT population consisted of all participants who had a wtKRAS tumor genotype. The efficacy analyses were planned for and only included participants from the DB portion of the study. Participants from the OL portion were excluded from the analyses. Participants were counted in the group to which they were randomized. | Posted | Number | Percentage of Participants | Every 6 weeks (Up to 32 months) |
|
|
|
| 94 |
| 180 |
| 178 |
| 180 |
| EG001 | Dalotuzumab 15 mg/kg /7.5 mg/kg Q2W (OL) | In the OL portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W + irinotecan Q1W at their pre-study dosage + OL dalotuzumab (loading dose of 15 mg/kg IV followed by a maintenance dose of 7.5 mg/kg 2 weeks later) to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. | 5 | 8 | 8 | 8 |
| EG002 | Dalotuzumab 10 mg/kg Q1W (OL) | In the OL portion of the study, ≥6 participants received cetuximab 400 mg/m^2 Q1W+ irinotecan Q1W at their pre-study dosage + OL dalotuzumab 10 mg/kg IV Q1W to verify the safety of the regimen. In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. | 4 | 10 | 10 | 10 |
| EG003 | Dalotuzumab 15 mg/kg /7.5 mg/kg Q2W (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. In DB Week 2, participants received cetuximab 250 mg/m^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. | 77 | 180 | 174 | 180 |
| EG004 | Placebo + Cetuximab + Irinotecan (DB) | In DB Week 1, participants received cetuximab 400 mg/m^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment. | 75 | 178 | 172 | 178 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Acute coronary syndrome | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Aortic valve stenosis | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Arrhythmia supraventricular | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Atrioventricular block complete | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
|
| Deafness bilateral | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
|
| Blindness transient | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Retinal detachment | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Anal fistula | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Anal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Colonic obstruction | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Enteritis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Faecaloma | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hiatus hernia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Intestinal perforation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Large intestine perforation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Peritonitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Subileus | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Death | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Systemic inflammatory response syndrome | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal abscess | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Abscess bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Bacterial sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Biliary sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Catheter site infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Clostridial infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Infected skin ulcer | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Isosporiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Klebsiella sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenic sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Pneumonia necrotising | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Pyelonephritis acute | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Rectal abscess | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Staphylococcal bacteraemia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Urinary tract infection bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Osteoporotic fracture | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Lymphangiosis carcinomatosa | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Altered state of consciousness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diabetic hyperosmolar coma | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Anuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Azotaemia | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Calculus ureteric | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Postrenal failure | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diaphragmatic hernia | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypovolaemic shock | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA 14.0 | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dark circles under eyes | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Erosive duodenitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rectal tenesmus | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Reflux oesophagitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Infusion site reaction | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Oesophageal candidiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Peritonitis bacterial | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Syphilis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Tongue injury | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Cachexia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Urinary hesitation | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 14.0 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| 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 |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| Hazard Ratio (HR) |
| 1.13 |
| 2-Sided |
| 95 |
| 0.83 |
| 1.55 |
| Superiority or Other |