Randomized, Placebo-Controlled, Double-Blind Phase 2 Study of mFOLFOX6 Chemotherapy Plus Ramucirumab Drug Product(IMC-1121B) Versus mFOLFOX6 Plus Placebo for Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach
Overview
- Phase
- Phase 2
- Intervention
- Ramucirumab
- Conditions
- Stomach Cancer
- Sponsor
- Eli Lilly and Company
- Enrollment
- 168
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study is to determine whether ramucirumab when used in conjunction with chemotherapy treatment can help participants with stomach, esophagus, and gastroesophageal cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic or cytologic confirmation of adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), or stomach
- •Metastatic or locally advanced, unresectable disease at time of study entry
- •Provided signed informed consent and is amenable to compliance with protocol schedules and testing
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 at study entry
- •Adequate renal, hematological, and hepatic function
- •Measurable or non-measurable disease at the time of study entry
- •Resolution to Grade less than or equal to 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy, except where otherwise mentioned in the eligibility criteria
- •Eligible participants of reproductive potential (both sexes) must agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and at least 12 weeks after the last dose of study therapy
- •Life expectancy of greater than or equal to 3 months
- •Willingness to provide blood and tissue samples for research purposes. Submission of tumor specimen is mandatory for participation in this study, if a histologic, paraffin-embedded specimen exists (either from a surgical resection or biopsy); submission of paraffin block or a minimum of 8 unstained slides is required if sufficient sample. NOTE: If insufficient additional tissue exists (that is, all tissue has been utilized for prior diagnostic purposes), participation in the study is allowable without the requirement for an additional biopsy; this situation must be discussed with the study principal investigator and/or the ImClone medical monitor or designee.
Exclusion Criteria
- •The participant has received prior first-line systemic therapy for advanced/unresectable and/or metastatic disease (prior adjuvant or neo-adjuvant therapy is permitted)
- •Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to study entry
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the participant ineligible for entry into this study
- •The participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (for example, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 milligrams per day (mg/day) is permitted.
- •The participant has significant third-space fluid retention (for example, ascites or pleural effusion), and is not amenable for required repeated drainage
- •The participant is pregnant or breastfeeding
- •Uncontrolled intercurrent illness including, but not limited to, active or uncontrolled clinically serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled thromboembolic, or hemorrhagic disorder, psychiatric illness/social situations, or other co-morbid systemic illnesses, or other severe concurrent disease
- •Immunocompromised participants including participants known to be human immunodeficiency virus (HIV) positive.
- •Progressive disease less than or equal to 12 months of completing platinum or 5-FU treatment, including capecitabine, if given previously in the perioperative (adjuvant or neoadjuvant) setting
- •Current or recent (within 28 days prior to randomization) treatment with an investigational drug that has not received regulatory approval for any indication at the time of study entry, or participation in another interventional clinical trial. Participants participating in surveys or observational studies are eligible to participate in this study.
Arms & Interventions
Ramucirumab
* Oxaliplatin 85 milligrams per square meter (mg/m\^2) given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-Fluorouracil (5-FU) 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: Ramucirumab
Ramucirumab
* Oxaliplatin 85 milligrams per square meter (mg/m\^2) given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-Fluorouracil (5-FU) 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: Oxaliplatin
Ramucirumab
* Oxaliplatin 85 milligrams per square meter (mg/m\^2) given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-Fluorouracil (5-FU) 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: Leucovorin
Ramucirumab
* Oxaliplatin 85 milligrams per square meter (mg/m\^2) given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-Fluorouracil (5-FU) 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: 5-Fluorouracil
Placebo
* Oxaliplatin 85 mg/m\^2 given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-FU 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Placebo given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: Placebo
Placebo
* Oxaliplatin 85 mg/m\^2 given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-FU 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Placebo given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: Oxaliplatin
Placebo
* Oxaliplatin 85 mg/m\^2 given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-FU 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Placebo given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: Leucovorin
Placebo
* Oxaliplatin 85 mg/m\^2 given on Day 1 of a 2-week cycle * Leucovorin 400 mg/m\^2 given on Day 1 of a 2-week cycle * 5-FU 400 mg/m\^2 bolus given on Day 1 of a 2-week cycle * 5-FU 2400 mg/m\^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle * Placebo given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met
Intervention: 5-Fluorouracil
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Randomization to measured PD or date of death from any cause (up to Month 25.0)
PFS was defined using Response Evaluation Criteria in Solid Tumors \[RECIST version (v.) 1.1\] as the time from randomization to the first observation of progressive disease (PD) or death due to any cause, whichever came first. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 millimeters (mm); the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. If a participant did not have a baseline disease assessment, PFS time was censored at the randomization date, regardless of whether or not PD or death was observed. Participants not known to have died or have objective PD were censored at the last post-baseline radiological assessment date.
Secondary Outcomes
- Time to Disease Progression (TTP)(Randomization to measured PD (up to Month 25.0))
- Duration of Response(Time of first response to measured PD (up to Month 23.0))
- Overall Survival (OS)(Randomization to date of death from any cause (up to Month 28.3))
- Percentage of Participants Achieving an Objective Response (Objective Response Rate)(Randomization to measured PD (up to Month 23.0))
- Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies(Months 1, 2, 4, 6, and 8)