A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer (RAINFALL)

Lilly

Status and phase: Completed; Phase 3

Conditions: Metastatic Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Treatments: Drug: Capecitabine; Drug: Placebo; Drug: Cisplatin; Drug: Ramucirumab; Drug: Fluorouracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT02314117

2014-002240-40 (EudraCT Number)

15372

I4T-MC-JVCU (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 645 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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645 participants in 2 patient groups

Ramucirumab + Cisplatin + Capecitabine

Experimental group

Description:

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 were 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.

Treatment:

Drug: Capecitabine

Drug: Ramucirumab

Drug: Cisplatin

Drug: Fluorouracil

Placebo + Cisplatin + Capecitabine

Active Comparator group

Description:

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 were 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.

Treatment:

Drug: Capecitabine

Drug: Placebo

Drug: Cisplatin

Drug: Fluorouracil