Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM)

February 20, 2017 updated by: H. Lee Moffitt Cancer Center and Research Institute

Phase I/II Trial of Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM)

The purpose of this research study was to evaluate how effective the combination of Carboplatin, Bevacizumab (Avastin™) and, Pemetrexed (Alimta™) is in the treatment of patients with Malignant Pleural Mesothelioma (MPM). A combination of cisplatin and pemetrexed is considered standard for this disease and typically off protocol patients would receive cisplatin or carboplatin and pemetrexed as standard of care.

The planned length of the study (first patient screened to last patient enrolled) was 24 months. The planned length of the entire study (enrollment period + the treatment period + a follow-up period of at least 12 months) was 36 months.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This was a planned Phase I/II dose escalation study. Patients were enrolled in a cohort of 3.

Eligible patients with unresectable pleural mesothelioma received frontline treatment consisting of carboplatin AUC 5, bevacizumab 15 mg/kg, and pemetrexed 500 mg/m^2 every 21 days (Tier-1). Dose escalation continued to achieve a target dosage using carboplatin AUC 6 (Tier-2). After a maximum of 6 treatment cycles, non-progressing patients received maintenance therapy with bevacizumab and pemetrexed every 21 days to complete 1-year total treatment duration.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient must have histologically proven diagnosis of Malignant Pleural Mesothelioma (MPM)
  • Patient must have MPM with measurable disease.
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Patient must have adequate renal function with a serum creatinine level of less than 1.5 mg/dl and patient should have a calculated creatinine clearance of more than 40ml/min.
  • Patient must have adequate hepatic function with a serum bilirubin level of less that 3mg/dl, and an alkaline phosphatase, ALT and AST of less than five times the upper limit of normal
  • Patient must also have evidence of adequate bone marrow function with an absolute neutrophil count of more than 1500 cells per deciliter and a platelet count of more than 100,000 per deciliter.
  • Patients must be more than 28 days since prior open biopsy; more than 7 days since prior fine-needle aspiration; more than 7 days since prior core biopsy; more than 28 days since prior surgery.
  • Patients must be able to take dexamethasone, folic acid, and vitamin B-12 supplementation.
  • All patients must sign informed consent that will detail the investigational nature of the study in accordance with the institutional and federal guidelines.
  • Patients with clinically significant pleural effusions or ascites (symptomatic or detectable by clinical exam) should have their effusions drained prior to enrollment on the clinical trial.

Exclusion Criteria:

  • Patients with hypercalcemia (corrected calcium of more than 11 mg/dl) will be excluded.
  • Patients with history of hemoptysis, haematemesis, coagulopathy or thrombosis will be excluded.
  • Patients requiring anticoagulation for any reason will be excluded.
  • History of palliative radiation therapy within 2 weeks
  • Blood pressure of >160/100 mmHg, despite adequate anti-hypertensive use.
  • Currently ongoing unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure.
  • History of stroke within 6 months
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the day of initiation of treatment, anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to the day of initiation of treatment.
  • Pregnant (positive pregnancy test) or lactating
  • Urine calculated creatinine clearance of less than 40ml/minute. - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
  • Serious, non-healing wound, ulcer, or bone fracture
  • Inability to comply with study and/or follow-up procedures

Laboratory Values:

  • Patient must have adequate renal function with a serum creatinine level of less than 1.5 mg/dl and patient should have a calculated creatinine clearance of more than 40ml/min.
  • Patient must have adequate hepatic function with a serum bilirubin level of less than 3 mg/dl, and an alkaline phosphatase, ALT and AST of less than five times the upper limit of normal
  • Patient must also have evidence of adequate bone marrow function with an absolute neutrophil count of more than 1, 500 cells per deciliter and a platelet count of more than 100,000 per deciliter.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Dose Escalation Followed by Maintenance Therapy

A: Tiered Dose Escalation/Phase II Dose -

  • Tier -1: Carboplatin AUC 4 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m^2.
  • Tier 1: Carboplatin AUC 5 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m^2.
  • Tier 2: Carboplatin AUC 6 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m^2.

B: Maintenance Therapy -

  • Patient was maintained on pemetrexed plus bevacizumab for a total of one year after initiation of maintenance or until progression which ever occured first.
Drug: Carboplatin, Bevacizumab and Pemetrexed
Chemotherapy was given for 2 cycles after maximal response. Patients were taken off study at the time of progression. If the patient had stable disease or better, as a response, then the patient was maintained on pemetrexed plus bevacizumab for a total of one year after initiation of maintenance or until progression which ever occured first. Computed tomography (CT) scans were be done every 12 weeks during the maintenance phase.
Other Names:
  • Bevacizumab (Avastin™)
  • Pemetrexed (Alimta™)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Partial Response (PR) of Target Lesions
Time Frame: Up to 12 Months
Tumor response was assessed in 12 patients who had at least one follow-up computed tomography (CT) scan. Response Evaluation Criteria in Solid Tumors (RECIST) definition of Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Up to 12 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Months of Progression Free Survival (PFS)
Time Frame: 2 Years, 9 Months
The PFS is defined as the duration of time from the start of treatment to time of progression or death, whichever occurs first.
2 Years, 9 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Tawee Tanvetyanon, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (ACTUAL)

January 1, 2011

Study Completion (ACTUAL)

January 1, 2011

Study Registration Dates

First Submitted

January 17, 2008

First Submitted That Met QC Criteria

January 29, 2008

First Posted (ESTIMATE)

January 30, 2008

Study Record Updates

Last Update Posted (ACTUAL)

March 23, 2017

Last Update Submitted That Met QC Criteria

February 20, 2017

Last Verified

November 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-14896
  • AVF3483s (OTHER: Genentech)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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