Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Malignant Mesothelioma

NCT00027703 | Completed Phase 2

• 8 other identifiers: NCI-2012-02430CDR0000069058NCI-2710UCCRC-11046A11046A2710N01CM17102P30CA014599
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial is to see if combination chemotherapy works better with or without bevacizumab in treating patients who have malignant mesothelioma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. It is not yet known if combination chemotherapy works better with or without bevacizumab in treating malignant mesothelioma.

Conditions

Advanced Malignant Mesothelioma; Epithelial Mesothelioma; Localized Malignant Mesothelioma; Recurrent Malignant Mesothelioma; Sarcomatous Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Time to disease progression

  The two treatment groups will be compared using a stratified logrank test. Kaplan-Meier time-to-event curves will be constructed for each treatment group. Median time-to-progression in each group and corresponding 95% confidence intervals will be derived using the method described in Brookmeyer and Crowley.

  Time from randomization until the first evidence of progression, up to 9 years

Secondary Outcomes (5)

• Complete response rate

  Up to 6 months

• Objective response rate (complete and partial response)

  Up to 6 months

• Rate of disease stabilization

  Up to 6 months

• Overall survival

  Up to 9 years

• Incidence of adverse events graded according to NCI CTCAE version 3.0

  Up to 9 years

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-60 minutes (beginning after gemcitabine infusion) and bevacizumab IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease (SD), complete response (CR), or partial response (PR) after the sixth course may receive bevacizumab as a single agent once every 3 weeks in the absence of disease progression or unacceptable toxicity.

Drug: gemcitabine hydrochloride; Drug: cisplatin; Biological: bevacizumab; Other: laboratory biomarker analysis

Arm II

EXPERIMENTAL

Patients receive gemcitabine and cisplatin as in arm I and placebo IV over 30-90 minutes (beginning after cisplatin infusion) on day 1. Treatment repeats as in arm I. Patients who achieve SD, CR, or PR after the sixth course may receive placebo as a single agent once every 3 weeks in the absence of disease progression.

Drug: gemcitabine hydrochloride; Drug: cisplatin; Other: placebo; Other: laboratory biomarker analysis

Interventions

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Arm I; Arm II

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Arm I; Arm II

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Arm I

placebo OTHER

Given IV

Also known as: PLCB

Arm II

laboratory biomarker analysis OTHER

Correlative studies

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma that is not amenable to curative surgery
• Epithelial, sarcomatoid, or mixed subtype
• Evidence of gross unresectability, including, but not limited to, the following conditions:
• Direct extension into the chest wall
• Mediastinal or hilar lymphadenopathy
• Pulmonary or cardiac function that is inadequate to tolerate resection
• Sarcomatoid or mixed histology
• Pleural mesothelioma must be stage II or greater using the International Mesothelioma Interest Group staging system
• Measurable disease outside prior irradiation port
• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Pleural effusions and ascites are not considered measurable lesions
• Site in pleura, lung, liver, or retroperitoneum that can be assessed by MRI for evaluation of blood flow
• No obvious tumor involvement of major vessels by CT scan
• No known brain metastases
• Performance status - ECOG 0-1

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Mesothelioma, Malignant; Solitary Fibrous Tumor, Pleural

Interventions

Gemcitabine; Cisplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Solitary Fibrous Tumors; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hedy Kindler

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2001
• First Posted: January 27, 2003
• Study Start: October 1, 2001
• Primary Completion: May 1, 2006
• Last Updated: February 11, 2014

Record last verified: 2012-12

Locations

US (1)