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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00084604
First received: June 10, 2004
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: irinotecan hydrochloride
Biological: bevacizumab
Drug: cisplatin
Procedure: computed tomography
Other: laboratory biomarker analysis
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to progression, evaluated using RECIST [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be used.


Secondary Outcome Measures:
  • Overall response rate, evaluated using RECIST [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    95% exact binomial confidence intervals will be used to describe the distribution.

  • Complete response rate, evaluated using RECIST [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    95% exact binomial confidence intervals will be used to describe the distribution.

  • Duration of response, evaluated using RECIST [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be used.

  • Incidence of toxicity, evaluated using CTCAE version 3.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 47
Study Start Date: April 2004
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Procedure: computed tomography
Correlative studies
Other Name: tomography, computed
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084604

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Manisha Shah Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00084604     History of Changes
Other Study ID Numbers: NCI-2012-01450, 04-021, NCI-6447, MSKCC-04021, CDR0000365463, N01CM17105, U01CA099168
Study First Received: June 10, 2004
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Bevacizumab
Irinotecan
Cisplatin
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014