Cisplatin, Pemetrexed and Bevacizumab for Untreated Malignant Mesothelioma

• ClinicalTrials.gov Identifier: NCT00295503
• Recruitment Status: Completed
• First Posted: February 23, 2006
• Results First Posted: January 5, 2017
• Last Update Posted: October 20, 2020
• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: University of Chicago; Columbia University; Duke University
• Information provided by (Responsible Party): University of Texas Southwestern Medical Center

Study Description

Brief Summary:

To estimate the time to progression of cancer in patients with previously untreated mesothelioma receiving cisplatin, pemetrexed and bevacizumab

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Drug: bevacizumab; Drug: cisplatin; Drug: pemetrexed	Phase 2

Detailed Description:

Secondary endpoints will include:

objective response rate

overall survival

In addition, the objective of the analysis of the correlative science data is to determine any association between tumor expression of VEGF/KDR complex and/or the presence of sv40 (as detected by PCR amplification) and objective response.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Cisplatin, Pemetrexed and Bevacizumab in Untreated Malignant Mesothelioma
• Study Start Date: February 2006
• Actual Primary Completion Date: June 2010
• Actual Study Completion Date: August 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; cisplatin, pemetrexed, and bevacizumab	Drug: bevacizumab; 15 mg/kg IV every 3 weeks; Drug: cisplatin; 75 mg/m2 IV every 3 weeks; Drug: pemetrexed; 500 mg/m2 every 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival Rate at 6 Months [ Time Frame: patients progression free at 6 months ]
   This is the percentage of patients alive and progression-free at 6 months from initiation of treatment.

Secondary Outcome Measures :

1. Response Rate [ Time Frame: from time of enrollment to time of best response or death from any cause, whichever came first up to 100 months ]
   response was assessed by the RECIST criteria (version 1.0). Per those criteria, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
2. Overall Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up 100 months ]
   overall survival was measured from time of initiation of treatment to death from any cause

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria

5.2.1 Patients must have histologically proven malignant mesothelioma (epithelial, sarcomatoid, or mixed subtype) not amenable to curative surgery or radiotherapy. Eligible sites of origin include the pleura, peritoneum, and tunica vaginalis.

5.2.2 Patient's disease must not be amenable to curative treatment with surgery. Evidence of gross unresectability will include but not be limited to direct extension into the chest wall, mediastinal or hilar lymphadenopathy, pulmonary or cardiac function that is inadequate to tolerate resection, and sarcomatoid or mixed histology.

5.2.3 Patients must be > 18 years old 5.2.4 Patients must have measurable disease.

Adequate organ function and functional status

Exclusion Criteria:

a. General Medical Concerns 5.3.1 Patients must not be pregnant or breast feeding. 5.3.2 No "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" second malignancy if they have completed therapy and have a less than 30% risk of relapse.

5.3.3 No uncontrolled intercurrent illness including but not limited to: active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social situations that would limit compliance with study requirements.

5.3.4 No HIV positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with study medications.

5.3.5 History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in the study.

5.3.6 Inability to interrupt aspirin or other non-steroidal medication for a 5 day period.

c. Bevacizumab-Specific Concerns

Subjects meeting any of the following criteria are ineligible for study entry:

5.3.7 Patients with brain metastases are excluded 5.3.8 History of myocardial infarction or CVA (stroke) within 6 months of study entry.

5.3.9 Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic doses of coumadin are eligible as long as the INR is maintained in the range of 2-3 and there is no evidence of active bleeding.

5.3.10 Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study 5.3.11 Urine protein:creatinine ratio less than 1.0 at screening 5.3.12 Serious, non-healing wound, ulcer, or bone fracture

Contacts and Locations

Locations

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390-8852

Sponsors and Collaborators

University of Texas Southwestern Medical Center

University of Chicago

Columbia University

Duke University

Investigators

• Principal Investigator: Jonathan E Dowell, MD; University of Texas

More Information

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00295503
• Other Study ID Numbers: AVF3442S
• First Posted: February 23, 2006
• Results First Posted: January 5, 2017
• Last Update Posted: October 20, 2020
• Last Verified: September 2020

Keywords provided by University of Texas Southwestern Medical Center:

mesothelioma; bevacizumab; chemotherapy

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; 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; Bevacizumab; Pemetrexed; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors