Overview

This trial is active, not recruiting.

Conditions metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma
Treatments ramucirumab, capecitabine, cisplatin, placebo, fluorouracil
Phase phase 3
Target VEGF
Sponsor Eli Lilly and Company
Start date January 2015
End date January 2017
Trial size 616 participants
Trial identifier NCT02314117, 15372, 2014-002240-40, I4T-MC-JVCU

Summary

The main purpose of this study is to evaluate the effectiveness of ramucirumab, which is a targeted antibody, in combination with capecitabine and cisplatin compared to capecitabine and cisplatin alone in participants with stomach cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m^2) cisplatin given IV on day 1 of each 21 day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that are unable to take capecitabine will be given 800 mg/m^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21 day cycle.
ramucirumab LY3009806
Administered IV
capecitabine
Administered orally
cisplatin
Administered IV
fluorouracil
Administered IV
(Active Comparator)
Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m^2 cisplatin given IV on day 1 of each 21 day cycle (for up to 6 cycles) and 1000 mg/m^2 capecitabine given orally twice a day on days 1 through 14. Participants that are unable to take capecitabine will be given 800 mg/m^2/day 5-FU IV on days 1 to 5 of each 21 day cycle.
capecitabine
Administered orally
cisplatin
Administered IV
placebo
Administered IV
fluorouracil
Administered IV

Primary Outcomes

Measure
Progression Free Survival (PFS)
time frame: Randomization to Radiological Disease Progression or Death from Any Cause (Approximately 42 Months)

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: Randomization to Death from Any Cause (Approximately 42 Months)
Progression Free Survival 2 (PFS2)
time frame: Randomization to Second Radiological or Symptomatic Disease Progression After the Start of Additional Systemic Anticancer Treatment or Death from Any Cause (Approximately 42 Months)
Objective Response Rate (ORR)
time frame: Randomization to Disease Progression (Approximately 42 Months)
Disease Control Rate (DCR)
time frame: Randomization to Disease Progression (Approximately 42 Months)
Time to Progression (TTP)
time frame: Randomization to Disease Progression (Approximately 42 Months)
Duration of Response (DoR)
time frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 42 Months)
Change from Randomization to 30 Days After Treatment Discontinuation in Quality of Life on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
time frame: Randomization, 30 Days After Treatment Discontinuation (Approximately 42 Months)
Change from Randomization to 30 Days After Treatment Discontinuation in Health Status on the European Quality of Life 5-Dimensions 5 Level Instrument (EQ-5D- 5L)
time frame: Randomization, 30 Days After Treatment Discontinuation (Approximately 42 Months)
Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
time frame: Randomization to ECOG PS ≥2 (Approximately 42 Months)
Pharmacokinetics (PK): Minimum Ramucirumab Concentration (Cmin) and Concentration at 1-Hour Post End of Ramucirumab Infusion (Approximately Maximum Concentration [Cmax])
time frame: Predose Cycle 1 through Cycle 9 (Approximately 6 Months)
Number of Participants with Anti-Ramucirumab Antibodies
time frame: Predose Cycle 1 through 30 Days After Treatment Discontinuation (Approximately 42 Months)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Have a histopathologically confirmed diagnosis of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. All histologies of nonsquamous cell origin including undifferentiated gastric carcinoma are eligible. - Have not received any prior first-line systemic therapy (prior adjuvant or neo-adjuvant therapy is permitted). Participants whose disease has progressed after >12 months following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible. - Have measurable or nonmeasurable but evaluable disease determined using guidelines in Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1). Baseline tumor assessment should be performed using a high resolution computed tomography (CT) scan using IV and oral contrast unless clinically contra-indicated. Magnetic resonance imaging (MRI) is acceptable if a CT cannot be performed. - Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale at baseline. - Have adequate organ function. - Have baseline clinical and laboratory parameters that are consistent with the requirements prescribed in respective labels and are suitable for consideration of treatment with capecitabine (or 5-FU) and cisplatin (for example, dihydropyrimidine dehydrogenase deficiency). - Have an estimated life expectancy of ≥12 weeks in the judgment of the investigator. Exclusion Criteria: - Participants with adenocarcinoma of the esophagus are excluded. - Participants with human epidermal growth factor receptor 2 (HER2)-positive status. - Participants receiving chronic therapy with nonsteroidal anti-inflammatory agents. - Have radiation therapy within 14 days prior to randomization. - Have documented brain metastases, leptomeningeal disease or uncontrolled spinal cord compression. - Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 12 weeks prior to randomization. - Have experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization. - Have symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia. - Have uncontrolled hypertension prior to initiating study treatment, despite antihypertensive intervention. - Have undergone major surgery within 28 days prior to randomization, or central venous access device placement within 7 days prior to first dose of study treatment, except if the procedure is minimally invasive (for example, introduction of peripherally inserted central catheter [PICC] line) and the investigator does not anticipate any significant bleeding. - Have a history of gastrointestinal perforation and/or fistulae within 6 months prior to randomization. - Have a history of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization. - Have an acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator. - The participant has: - cirrhosis at a level of Child-Pugh B (or worse) or - cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis. - Have known allergy or hypersensitivity to any components of study treatment. - Are pregnant or lactating.

Additional Information

Official title A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Capecitabine and Cisplatin With or Without Ramucirumab as First-line Therapy in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (RAINFALL)
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.