Overview

This trial is active, not recruiting.

Conditions gastric cancer, adenocarcinoma
Treatments imc-1121b (ramucirumab), placebo, best supportive care (bsc)
Phase phase 3
Sponsor Eli Lilly and Company
Start date August 2009
End date July 2012
Trial size 355 participants
Trial identifier NCT00917384, 13893, 2008-005964-15, CP12-0715, I4T-IE-JVBD

Summary

The purpose of this study is to gather information about the use of an investigational drug called IMC-1121B (Ramucirumab) in adenocarcinomas of the gastroesophageal junction.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants receive IMC-1121B (ramucirumab), administered via intravenous infusion every 2 weeks at a dose of 8 milligrams/kilogram (mg/kg), and best supportive care (BSC) as determined appropriate by the investigator(s). Treatment will continue until there is evidence of progressive disease (PD), the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
imc-1121b (ramucirumab) IMC-1121B
Administered via intravenous infusion every 2 weeks at a dose of 8 mg/kg
best supportive care (bsc)
BSC as determined appropriate by the investigator(s). BSC may include but are not limited to antiemetic agents, opiate and nonopiate analgesic agents, appetite stimulants, and granulocyte and erythroid growth factors.
(Placebo Comparator)
Participants receive injection for intravenous infusion every 2 weeks plus BSC as determined appropriate by the investigator(s). Because investigators and ancillary medical personnel will be blinded as to assignment to active therapy versus placebo, the volume of placebo to be administered will be calculated as if it were active product with a dose of 8 mg/kg. Treatment will continue until there is evidence of PD, the development of unacceptable toxicity, protocol noncompliance, or withdrawal of consent.
placebo
Placebo comparator for IMC-1121B (ramucirumab) 8 mg/kg as intravenous infusion every 2 weeks
best supportive care (bsc)
BSC as determined appropriate by the investigator(s). BSC may include but are not limited to antiemetic agents, opiate and nonopiate analgesic agents, appetite stimulants, and granulocyte and erythroid growth factors.

Primary Outcomes

Measure
Overall Survival (OS)
time frame: Approximately 30 months

Secondary Outcomes

Measure
Proportion of Participants Who are Progression-free (PFS) at Week 12
time frame: Week 12
Proportion of Participants with Objective Response (Objective Response Rate)
time frame: Approximately 30 months
Duration of Response
time frame: Approximately 30 Months
Change from Baseline in Quality of Life (QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ-C30) Survey
time frame: 18 Weeks
Number of Participants with Adverse Events
time frame: Approximately 30 Months
Maximum concentration (Cmax) of IMC-1121B
time frame: 6 weeks
Change from Baseline in Antibodies against IMC-1121B
time frame: 12 Weeks
Progression-free Survival (PFS)
time frame: Approximately 30 Months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically confirmed gastric carcinoma, including gastric adenocarcinoma or GEJ adenocarcinoma - Metastatic disease or locally recurrent, unresectable disease with measurable lymph node metastases - Measurable disease and/or evaluable disease. Measurable disease is defined as at least one unidimensionally-measurable target lesion [≥ 2 centimeter (cm) with conventional techniques or ≥ 1 cm by spiral computed tomography (CT)], as defined by Response using Response Evaluation Criteria in Solid Tumors (RECIST). Examples of evaluable, nonmeasurable disease include gastric, peritoneal, or mesenteric thickening in areas of known disease, or peritoneal nodules that are too small to be considered measurable by RECIST - Experienced disease progression during or within 4 months after the last dose of first-line therapy for metastatic disease, or during or within 6 months after the last dose of adjuvant therapy - Disease is not amenable to potentially curative resection - Participant is ≥ 18 years of age - Participant has a life expectancy of ≥ 12 weeks - Participant resolution to Grade ≤ 1 (or to Grade ≤ 2 in the case of neuropathy) by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia) - Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 - The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 milligrams/deciliter (mg/dL) [25.65 micromole/liter (µmol/L)], and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x the upper limit of normal (ULN) [or 5.0 x the ULN in the setting of liver metastases] - The participant has adequate renal function as defined by a serum creatinine ≤ 1.5 x the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥ 40 milliliters/minute (mL/min) (that is, if serum creatinine is > 1.5 x the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed) - The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis ([UA]; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study) - The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥ 1000 microliters (µL), hemoglobin ≥ 9 grams/deciliter (g/dL) [5.58 millimoles/liter (mmol/L)], and platelets ≥ 100,000/µL - The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Participant on anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection are not eligible - If the participant has received prior anthracycline therapy as part of his or her first-line regimen, the participant is able to engage in ordinary physical activity without significant fatigue or dyspnea - Because the teratogenicity of IMC-1121B is not known, the participant, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods) - Female participant of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization - Able to provide informed written consent and is amenable to compliance with protocol schedules and testing Exclusion Criteria: - Documented and/or symptomatic brain or leptomeningeal metastases - Experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to randomization - Experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to randomization - Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator - Ongoing or active psychiatric illness or social situation that would limit compliance with study requirements - Uncontrolled or poorly-controlled hypertension despite standard medical management - Participant has a serious or nonhealing wound, ulcer, or bone fracture - Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer within 2 weeks prior to randomization - Received any investigational therapy within 30 days prior to randomization - Undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization - Received prior therapy with an agent that directly inhibits vascular endothelial growth factor (VEGF) or VEGF receptor 2 (R-2) activity (including bevacizumab), or any antiangiogenic agent - Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use [maximum dose 325 milligram/day (mg/day)] is permitted - Participant has elective or planned major surgery to be performed during the course of the clinical trial - Participant has a known allergy to any of the treatment components - Pregnant or lactating - Known to be positive for infection with the human immunodeficiency virus - Known alcohol or drug dependency - Participant has a concurrent active malignancy other than adequately-treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been free of disease for > 3 years

Additional Information

Official title A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy
Description Placebo-controlled, multicenter Phase 3 study of participants with metastatic gastric cancer [including adenocarcinomas of the gastroesophageal junction (GEJ)] and disease progression on standard first-line chemotherapeutic regimens. Participants will be randomized on a 2:1 basis to receive best supportive care plus IMC-1121B administered every 2 weeks or best supportive care plus placebo administered every 2 weeks, respectively. Participants will undergo radiographic assessment of disease status every 6 weeks. Participant will be treated until there is evidence of progressive disease, toxicity requiring cessation, withdrawal of consent, or until other withdrawal criteria are met. Approximately 348 participants, with histologically- or cytologically-confirmed, metastatic gastric or GEJ adenocarcinoma, and radiographically measurable disease as defined by the Response Evaluation Criteria in Solid Tumors or evaluable, nonmeasurable disease, will be randomized. Participants will be enrolled from approximately 250 study centers in North America, South America, Central America, Asia, Australia, New Zealand, and Europe.
Trial information was received from ClinicalTrials.gov and was last updated in May 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.