Description:
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.
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.
Completed
Phase 3
NCT ID: NCT02314117
ORG ID: 15372
NCI ID: I4T-MC-JVCU
Metastatic Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Drug | Synonyms | Arms |
---|---|---|
Ramucirumab | LY3009806, IMC-1121B, Cyramza | Ramucirumab + Cisplatin + Capecitabine |
Capecitabine | Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine | |
Cisplatin | Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine | |
Placebo | Placebo + Cisplatin + Capecitabine | |
Fluorouracil | Ramucirumab + Cisplatin + Capecitabine, Placebo + Cisplatin + Capecitabine |
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.
Name | Type | Description | Interventions |
---|---|---|---|
Ramucirumab + Cisplatin + Capecitabine | 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, Capecitabine, Cisplatin, Fluorouracil |
Placebo + Cisplatin + Capecitabine | 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, Cisplatin, Placebo, Fluorouracil |
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.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Progression Free Survival (PFS)
Overall Survival (OS)
Progression Free Survival 2 (PFS2)
Objective Response Rate (ORR)
Disease Control Rate (DCR)
Time to Progression (TTP)
Duration of Response (DoR)
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)
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 to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Pharmacokinetics (PK): Minimum Ramucirumab Concentration (Cmin) and Concentration at 1-Hour Post End of Ramucirumab Infusion (Approximately Maximum Concentration [Cmax])
Number of Participants with Anti-Ramucirumab Antibodies