Resumen

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.

Descripción detallada

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 ramucirumab 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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Able to provide informed written consent and is amenable to compliance with protocol schedules and testing
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

Criterios de exclusión

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

Intervenciones

biological

ramucirumab

Administered via intravenous infusion every 2 weeks at a dose of 8 mg/kg

drug

Placebo

Placebo comparator for ramucirumab 8 mg/kg as intravenous infusion every 2 weeks

other

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.

Ubicaciones

ImClone Investigational Site

Buenos Aires, Argentina

ImClone Investigational Site

Buenos Aires, Argentina

ImClone Investigational Site

Capital Federal, Argentina

ImClone Investigational Site

Ciudada Autonoma, Argentina

ImClone Investigational Site

Córdoba, Argentina

ImClone Investigational Site

Rosario, Argentina

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

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

ramucirumab

Placebo

Best Supportive Care (BSC)

Ubicaciones

ImClone Investigational Site

ImClone Investigational Site

ImClone Investigational Site

ImClone Investigational Site

ImClone Investigational Site

ImClone Investigational Site

Patrocinadores