Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma
Condition: Gastric Cancer; Adenocarcinoma
MeSH terms: Adenocarcinoma; Stomach Neoplasms
Intervention: ramucirumab; Placebo; Best Supportive Care (BSC)
Intervention description: Administered via intravenous infusion every 2 weeks at a dose of 8 mg/kg; Placebo comparator for ramucirumab 8 mg/kg as intravenous infusion every 2 weeks; 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.
Intervention MeSH terms: Ramucirumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 355.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: IMC-1121B; Monoclonal antibody (MAb); Vascular endothelial growth factor (VEGF); Human vascular endothelial growth factor receptor-2 (VEGFR-2); Platinum resistant; platinum refractory; Gastric; Gastroesophageal Junction Adenocarcinoma; metastatic; Angiogenesis

Summary:

      The purpose of this study is to gather information about the use of an investigational drug
      called Ramucirumab in adenocarcinomas of the stomach or gastroesophageal junction.
    

Eligibility criteria:

        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