Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

NCT ID: NCT00084604

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30

Brief Summary

This phase II trial is studying how well giving irinotecan and cisplatin together with bevacizumab works in treating patients with unresectable or metastatic gastric (stomach) or gastroesophageal junction adenocarcinoma (cancer). Drugs used in chemotherapy, such as irinotecan and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Giving chemotherapy together with a monoclonal antibody may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the efficacy of irinotecan, cisplatin, and bevacizumab, in terms of time to progression, in patients with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

SECONDARY OBJECTIVES:

I. Determine other measures of efficacy, including response rate and median and 1-year survival, in patients treated with this regimen.

II. Determine the toxicity of this regimen in these patients. III. Correlate CT perfusion imaging results with the efficacy of this regimen, in terms of time to progression, objective response, and survival, in these patients.

IV. Determine the feasibility of serial serum proteomic assays in predicting response to therapy, in terms of time to progression, objective response, and survival, in patients treated with this regimen.

V. To bank paraffin stored tumor biopsy material for future planned immunohistochemistry studies to correlate with sensitivity to bevacizumab based combination chemotherapy.

OUTLINE: This is an open-label, non-randomized, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year.

Conditions

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (bevacizumab, cisplatin, irinotecan)

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive cisplatin IV over 30 minutes followed by irinotecan IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

bevacizumab

Intervention Type: BIOLOGICAL

Given IV

cisplatin

Intervention Type: DRUG

Given IV

computed tomography

Intervention Type: PROCEDURE

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

bevacizumab

Given IV

Intervention Type: BIOLOGICAL

cisplatin

Given IV

Intervention Type: DRUG

computed tomography

Correlative studies

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Campto; Camptosar; CPT-11; irinotecan; U-101440E; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF; CACP; CDDP; CPDD; DDP; tomography, computed

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma

• Metastatic or unresectable disease
• Siewert's classification I, II, or III
• No ulcerated, non-healing tumors or tumors that have developed a malignant fistula
• No esophageal tumors
• No known or active brain metastases
• Performance status - Karnofsky 60-100%
• Performance status - ECOG 0-2
• Neutrophil count >= 1,500/mm^3
• Platelet count >= 75,000/mm^3
• No bleeding diathesis or coagulopathy
• Bilirubin =< 1.5 mg/dL
• AST and ALT =< 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• PT (INR) =< 1.5
• PTT =< 3 seconds above ULN
• Creatinine =< 1.5 mg/dL
• Proteinuria < 1+
• Protein < 500 mg/24-hour urine collection
• No acute ischemia or significant conduction abnormality by EKG
• No clinically significant cardiovascular disease
• No uncontrolled hypertension (blood pressure > 160/90 mm Hg on medication)
• No myocardial infarction within the past 6 months
• No unstable angina within the past 6 months
• No transient ischemic attack within the past 6 months
• No cerebrovascular accident within the past 6 months
• No other arterial thromboembolic event within the past 6 months
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac dysrhythmia requiring medication
• No peripheral vascular disease (grade II or greater)
• No history of stroke
• No CNS disease within the past 5 years (e.g., uncontrolled seizures)
• No other concurrent uncontrolled illness
• No ongoing or active infection requiring parental antibiotics on Day 0 of study
• No serious, non-healing wound
• No serious wound healing by secondary intention
• No ulcer
• No bone fracture
• No psychiatric illness or social situation that would preclude study compliance
• No significant traumatic injury within the past 28 days
• No other neoplastic disease within the past 3 years except basal cell skin cancer, carcinoma in situ of the cervix, or nonmetastatic prostate cancer
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No other medical condition that would preclude study participation
• Not pregnant or nursing

• No nursing during and for 4 months after study participation
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 months after study participation
• More than 8 weeks since prior immunotherapy and recovered
• No other concurrent biologic or immunologic agents
• No other concurrent bevacizumab
• No prior chemotherapy for metastatic disease
• No prior cisplatin or irinotecan
• Prior neoadjuvant and/or adjuvant chemotherapy or chemoradiotherapy allowed
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy
• More than 3 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy
• More than 28 days since prior major surgical procedure or open biopsy
• More than 7 days since prior fine needle aspirations or core biopsies
• No concurrent major surgery
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent chronic daily aspirin (> 325 mg/day)
• No concurrent nonsteroidal anti-inflammatory medications that would inhibit platelet function at doses used to treat chronic inflammatory diseases
• Full-dose anticoagulants allowed, provided the following criteria are met:

• INR in range (i.e., 2-3) while on a stable dose of warfarin or low molecular weight heparin
• No active bleeding or pathologic condition that would confer a high risk of bleeding (e.g., tumor involving major blood vessels or known varices)
• No concurrent thrombolytic agents
• No concurrent vitamins, antioxidants, herbal preparations, or supplements

• Single tablet multivitamin allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manisha Shah

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

04-021

Identifier Type: -

Identifier Source: secondary_id

NCI-6447

Identifier Type: -

Identifier Source: secondary_id

MSKCC-04021

Identifier Type: -

Identifier Source: secondary_id

CDR0000365463

Identifier Type: -

Identifier Source: secondary_id

N01CM17105

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA099168

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01450

Identifier Type: -

Identifier Source: org_study_id