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

Adenocarcinoma of the Gastroesophageal Junction Clinical Trial

Official title:

A Multicenter, Open-Label, Phase II Study of Irinotecan, Cisplatin, and Bevacizumab in Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00084604
• Other study ID #: NCI-2012-01450
• Secondary ID: 04-021NCI-6447MS
• Status: Completed
• Phase: Phase 2
• First received: June 10, 2004
• Last updated: June 3, 2013
• Start date: April 2004

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Diffuse Adenocarcinoma of the Stomach
• Esophageal Neoplasms
• 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
• Stomach Neoplasms

Intervention

Drug:
• irinotecan hydrochloride
Given IV

Biological:
• bevacizumab
Given IV

Drug:
• cisplatin
Given IV

Procedure:
• computed tomography
Correlative studies

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression, evaluated using RECIST	Kaplan-Meier estimates will be used.	Up to 1 year	No
Secondary	Overall response rate, evaluated using RECIST	95% exact binomial confidence intervals will be used to describe the distribution.	Up to 1 year	No
Secondary	Complete response rate, evaluated using RECIST	95% exact binomial confidence intervals will be used to describe the distribution.	Up to 1 year	No
Secondary	Duration of response, evaluated using RECIST		From the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 1 year	No
Secondary	Survival	Kaplan-Meier estimates will be used.	Up to 1 year	No
Secondary	Incidence of toxicity, evaluated using CTCAE version 3.0		Up to 1 year	Yes