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

Phase 1

• Conditions: Metastatic gastric adenocarcinoma or gastroesophageal junction (GEJ) denocarcinoma; MedDRA version: 20.0Level: PTClassification code 10063916Term: Metastatic gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002240-40-FI
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-13
• Last Update Posted: 6 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 616

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 370
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 246

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:
ocirrhosis at a level of Child-Pugh B (or worse) or
ocirrhosis (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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: compare PFS of ramucirumab in combination with capecitabine (or 5-fluorouracil [5-FU]) and cisplatin versus placebo in combination with capecitabine (or 5-FU) and cisplatin as first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma;Secondary Objective: •Overall survival<br>•Progression Free Survival 2 (PFS2)<br>•Objective Response Rate<br>•Disease Control Rate<br>•Time to Progression<br>•Duration of Response<br>•Change from baseline in quality of life on the EORTC QLC-C30<br>•Change from baseline in health status on the EuroQol EQ-5D<br>•Pharmacokinetics: minimum and maximum concentration of ramucirumab<br>•Immunogenicity: number of participants with anti-ramucirumab antibodies<br>•Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)<br>;Primary end point(s): Progression Free Survival (PFS);Timepoint(s) of evaluation of this end point: After 484 PFS events for approximately 616 patients have been reported.