Colorectal Cancer
Conditions
Keywords
second line, metastatic colorectal cancer, FOLFIRI, ramucirumab, CRC, mCRC
Brief summary
The purpose of this study is to compare overall survival in participants with metastatic colorectal cancer treated with either ramucirumab and FOLFIRI or placebo and FOLFIRI.
Interventions
BIOLOGICALRamucirumab
8 milligrams / kilogram (mg/kg) administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the participant or investigator decision
BIOLOGICALPlacebo
Administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the participant or investigator decision
DRUGIrinotecan
180 milligrams/square meter (mg/m\^2) administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the participant or investigator decision
DRUGFolinic Acid
400 mg/m\^2 administered intravenously every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the participant or investigator decision
DRUG5-Fluorouracil
400 mg/m\^2 bolus immediately followed by 2400 mg/m\^2 continuous infusion every 2 weeks until disease progression, unacceptable toxicity, noncompliance or withdrawal of consent by the participant or investigator decision
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed colorectal cancer, excluding primary tumors of appendiceal origin (participants are eligible to enroll irrespective of KRAS mutation status) * Confirmed metastatic colorectal cancer (Stage IV) * The participant has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and, a) Experienced radiographic disease progression during first-line therapy, or b) Experienced radiographic disease progression ≤6 months after the last dose of first-line therapy, or c) Discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression ≤6 months after the last dose of first-line therapy. Note that a participant must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy; in addition, a participant must have received at least 1 cycle of first-line therapy that included bevacizumab, oxaliplatin and a fluoropyrimidine in the same cycle. Note that a participant must not have received more than 2 different fluoropyrimidines as part of a first-line regimen; disease progression is not an acceptable reason for discontinuing 1 fluoropyrimidine and starting a second fluoropyrimidine * Receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted). For participants with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen. Note that rechallenge with oxaliplatin is permitted and will be considered part of the first-line regimen for metastatic disease, both initial oxaliplatin treatment and subsequent rechallenge are considered as 1 regimen * Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Adequate hematologic, renal and hepatic function * Adequate coagulation function \[International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x upper limit of normal (ULN)). Participants on full-dose anticoagulation must be on a stable dose of anticoagulant therapy and if on oral anticoagulation, must have an INR ≤3 and have no clinically significant active bleeding or pathological condition that carries a high risk of bleeding * Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available * Ability to provide signed informed consent
Exclusion criteria
* Receipt of bevacizumab ≤28 days prior to randomization * Receipt of any investigational therapy for non-oncology clinical indication ≤28 days prior to randomization * Receipt of any previous systemic therapy, other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine, for first-line treatment of metastatic colorectal cancer * Known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression (currently or in the past) * Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to, myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤12 months prior to randomization * Pregnant (confirmed by serum beta human chorionic gonadotropin (ß HCG) test ≤7 days prior to randomization) or lactating * History of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization * Acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator * Grade 3 or higher bleeding event ≤3 months prior to randomization * Experience of any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event, Grade 4 hypertension, Grade 3 proteinuria, a Grade 3-4 bleeding event, or bowel perforation * Known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: UGT1A1\*6/\*6, UGT1A1\*28/\*28, or UGT1A1\*6/\*28 * Known allergy to any of the study treatment components, including any components used in the preparation of ramucirumab, or other contraindication to receive the study treatments * Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Randomization to Date of Death from Any Cause Up to 39.36 Months | OS was defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last known date alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Objective Response (Objective Response Rate) | Randomization until Disease Progression Up to 38.01 Months | The objective response rate is equal to the proportion of participants achieving a best overall response of partial response or complete response (PR + CR). Response was defined using RECIST, v. 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameter. |
| Change From Baseline in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 Global Health Status | Baseline Up to 171 Weeks | The EORTC QLQ-C30 (v. 3.0) is a self-administered, cancer-specific questionnaire with multidimensional scales assessing 15 domains (5 functional domains, 9 symptoms, and global health status). A linear transformation was applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptom scales, higher scores represent a greater degree of symptoms. Maximum improvement is the best post-baseline change. |
| Progression-free Survival (PFS) Time | Randomization to Measured PD or Date of Death from Any Cause Up to 38.01 Months | PFS was defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) \[according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1\] or death due to any cause, whichever was first. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment. |
| Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies | Cycles 1, 3, 5, and 30-Day FU | Blood samples were tested to determine if a participant reacted to ramucirumab by producing anti-ramucirumab antibodies. Samples were identified as treatment emergent anti-drug antibody (TE ADA) if the post-treatment sample had an increase of at least 4 fold in titer from pre-treatment values. If the pre-treatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence. The percentage of participants with TE ADA was calculated as: (the number of participants with TE ADA / total number of participants with at least 1 post-treatment immunogenicity sample analyzed)\*100. |
| Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Preinfusion and 1 hour postinfusion in Cycles 3, 5, 9, 13, and 17 | — |
| Change From Baseline in EuroQol- 5D (EQ-5D) | Baseline and 30-Day Follow-Up (FU) up to 171 Weeks | The EQ-5D is a generic, multidimensional, health status instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Netherlands, Portugal, Puerto Rico, Romania, Slovenia, South Korea, Spain, Sweden, Taiwan, United States
Participant flow
Pre-assignment details
Completers included participants who died from any cause and participants who were alive and on study at conclusion however were off treatment.
Participants by arm
| Arm | Count |
|---|---|
| Ramucirumab + FOLFIRI On Day 1 of each 14-day cycle, participants received ramucirumab followed by other study treatment in the following sequence: Irinotecan, Folinic Acid and 5-Fluorouracil. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.
Ramucirumab: 8 mg/kg administered intravenously.
Irinotecan: 180 mg/m\^2 administered intravenously.
Folinic Acid: 400 mg/m\^2 administered intravenously.
5-Fluorouracil: 400 mg/m\^2 bolus immediately followed by 2400 mg/m\^2 continuous infusion. | 536 |
| Placebo + FOLFIRI On Day 1 of each 14-day cycle, participants received placebo followed by other study treatment in following sequence: Irinotecan, Folinic Acid and 5-Fluorouracil. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.
Placebo: Administered intravenously.
Irinotecan: 180 mg/m\^2 administered intravenously.
Folinic Acid: 400 mg/m\^2 administered intravenously.
5-Fluorouracil: 400 mg/m\^2 bolus immediately followed by 2400 mg/m\^2 continuous infusion. | 536 |
| Total | 1,072 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 11 |
| Overall Study | Withdrawal by Subject | 25 | 14 |
Baseline characteristics
| Characteristic | Ramucirumab + FOLFIRI | Placebo + FOLFIRI | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 212 Participants | 215 Participants | 427 Participants |
| Age, Categorical Between 18 and 65 years | 324 Participants | 321 Participants | 645 Participants |
| Age, Continuous | 62.0 years | 62.0 years | 62.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 39 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 248 Participants | 221 Participants | 469 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 250 Participants | 276 Participants | 526 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 111 Participants | 103 Participants | 214 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 16 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) White | 405 Participants | 410 Participants | 815 Participants |
| Region of Enrollment Argentina | 7 Participants | 11 Participants | 18 Participants |
| Region of Enrollment Australia | 16 Participants | 19 Participants | 35 Participants |
| Region of Enrollment Austria | 6 Participants | 12 Participants | 18 Participants |
| Region of Enrollment Belgium | 30 Participants | 22 Participants | 52 Participants |
| Region of Enrollment Brazil | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Czech Republic | 40 Participants | 37 Participants | 77 Participants |
| Region of Enrollment Denmark | 3 Participants | 8 Participants | 11 Participants |
| Region of Enrollment Finland | 9 Participants | 3 Participants | 12 Participants |
| Region of Enrollment France | 12 Participants | 15 Participants | 27 Participants |
| Region of Enrollment Germany | 19 Participants | 25 Participants | 44 Participants |
| Region of Enrollment Greece | 8 Participants | 8 Participants | 16 Participants |
| Region of Enrollment Hungary | 24 Participants | 23 Participants | 47 Participants |
| Region of Enrollment India | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Israel | 7 Participants | 7 Participants | 14 Participants |
| Region of Enrollment Italy | 17 Participants | 20 Participants | 37 Participants |
| Region of Enrollment Japan | 74 Participants | 62 Participants | 136 Participants |
| Region of Enrollment Korea, Republic of | 22 Participants | 25 Participants | 47 Participants |
| Region of Enrollment Netherlands | 9 Participants | 5 Participants | 14 Participants |
| Region of Enrollment Portugal | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Puerto Rico | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Romania | 19 Participants | 14 Participants | 33 Participants |
| Region of Enrollment Spain | 51 Participants | 60 Participants | 111 Participants |
| Region of Enrollment Sweden | 10 Participants | 4 Participants | 14 Participants |
| Region of Enrollment Taiwan | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment United States | 141 Participants | 142 Participants | 283 Participants |
| Sex: Female, Male Female | 247 Participants | 210 Participants | 457 Participants |
| Sex: Female, Male Male | 289 Participants | 326 Participants | 615 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 518 / 529 | 510 / 528 |
| serious Total, serious adverse events | 198 / 529 | 175 / 528 |
Outcome results
Primary
Overall Survival (OS)
OS was defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last known date alive.
Time frame: Randomization to Date of Death from Any Cause Up to 39.36 Months
Population: All randomized participants. Participants censored: Ramucirumab + FOLFIRI group = 164; Placebo + FOLFIRI= 139.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab + FOLFIRI | Overall Survival (OS) | 13.3 months |
| Placebo + FOLFIRI | Overall Survival (OS) | 11.7 months |
p-value: 0.021995% CI: [0.73, 0.976]Log Rank
Secondary
Change From Baseline in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 Global Health Status
The EORTC QLQ-C30 (v. 3.0) is a self-administered, cancer-specific questionnaire with multidimensional scales assessing 15 domains (5 functional domains, 9 symptoms, and global health status). A linear transformation was applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptom scales, higher scores represent a greater degree of symptoms. Maximum improvement is the best post-baseline change.
Time frame: Baseline Up to 171 Weeks
Population: All randomized participants who had EORTC QLQ-C30 assessed at baseline and post-baseline .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramucirumab + FOLFIRI | Change From Baseline in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 Global Health Status | 4.0 units on a scale | Standard Deviation 20.61 |
| Placebo + FOLFIRI | Change From Baseline in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 Global Health Status | 6.6 units on a scale | Standard Deviation 18.84 |
Secondary
Change From Baseline in EuroQol- 5D (EQ-5D)
The EQ-5D is a generic, multidimensional, health status instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status.
Time frame: Baseline and 30-Day Follow-Up (FU) up to 171 Weeks
Population: All randomized participants who had EQ-5D assessed at baseline and 30-day FU.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramucirumab + FOLFIRI | Change From Baseline in EuroQol- 5D (EQ-5D) | -0.097 units on a scale | Standard Deviation 0.279 |
| Placebo + FOLFIRI | Change From Baseline in EuroQol- 5D (EQ-5D) | -0.103 units on a scale | Standard Deviation 0.264 |
Secondary
Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab
Time frame: Preinfusion and 1 hour postinfusion in Cycles 3, 5, 9, 13, and 17
Population: All randomized participants who received at least one dose of study drug and had evaluable data for Cmin and Cmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmin Dose 3 (n=248) | 46.3 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 45 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmin Dose 5 (n=154) | 65.1 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 43 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmin Dose 9 (n=27) | 77.9 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 51 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmin Dose 13 (n=11) | 75.9 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 43 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmin Dose 17 (n=5) | 72.0 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 49 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmax Dose 3 (n=88) | 221.0 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 37 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmax Dose 5 (n=51) | 243.0 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 39 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmax Dose 9 (n=18) | 262.0 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 36 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmax Dose 13 (n=12) | 307.0 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 33 |
| Ramucirumab + FOLFIRI | Observed Maximum Concentration (Cmax) and Observed Minimum Concentration (Cmin) of Ramucirumab | Cmax Dose 17 (n=7) | 253.0 micrograms/milliliter (ug/mL) | Geometric Coefficient of Variation 19 |
Secondary
Percentage of Participants Achieving an Objective Response (Objective Response Rate)
The objective response rate is equal to the proportion of participants achieving a best overall response of partial response or complete response (PR + CR). Response was defined using RECIST, v. 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameter.
Time frame: Randomization until Disease Progression Up to 38.01 Months
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab + FOLFIRI | Percentage of Participants Achieving an Objective Response (Objective Response Rate) | 13.4 percentage of participants |
| Placebo + FOLFIRI | Percentage of Participants Achieving an Objective Response (Objective Response Rate) | 12.5 percentage of participants |
p-value: 0.6336Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
Blood samples were tested to determine if a participant reacted to ramucirumab by producing anti-ramucirumab antibodies. Samples were identified as treatment emergent anti-drug antibody (TE ADA) if the post-treatment sample had an increase of at least 4 fold in titer from pre-treatment values. If the pre-treatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence. The percentage of participants with TE ADA was calculated as: (the number of participants with TE ADA / total number of participants with at least 1 post-treatment immunogenicity sample analyzed)\*100.
Time frame: Cycles 1, 3, 5, and 30-Day FU
Population: All participants who received study treatment and who had immunogenicity samples analyzed at the specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ramucirumab + FOLFIRI | Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies | Immunogenicity Any Time During Study (n=516, 512) | 5.6 percentage of participants |
| Ramucirumab + FOLFIRI | Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies | Immunogenicity Post-Treatment (n=477, 473) | 3.1 percentage of participants |
| Placebo + FOLFIRI | Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies | Immunogenicity Any Time During Study (n=516, 512) | 5.5 percentage of participants |
| Placebo + FOLFIRI | Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies | Immunogenicity Post-Treatment (n=477, 473) | 3.8 percentage of participants |
Secondary
Progression-free Survival (PFS) Time
PFS was defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) \[according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1\] or death due to any cause, whichever was first. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment.
Time frame: Randomization to Measured PD or Date of Death from Any Cause Up to 38.01 Months
Population: All randomized participants. Participants censored: Ramucirumab + FOLFIRI = 60; Placebo + FOLFIRI = 42.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab + FOLFIRI | Progression-free Survival (PFS) Time | 5.7 months |
| Placebo + FOLFIRI | Progression-free Survival (PFS) Time | 4.5 months |
p-value: 0.000595% CI: [0.697, 0.903]Log Rank