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

Brief Title

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

Official Title

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

Brief Summary

      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.
    

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 Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Number of Participants With Partial Response (PR) of Target Lesions

Secondary Outcome

 Number of Months of Progression Free Survival (PFS)

Condition

Mesothelioma

Intervention

Carboplatin, Bevacizumab and Pemetrexed

Study Arms / Comparison Groups

 Dose Escalation Followed by Maintenance Therapy

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

13

Start Date

October 2007

Completion Date

January 2011

Primary Completion Date

January 2011

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Tawee Tanvetyanon, M.D., , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00604461

Organization ID

MCC-14896

Secondary IDs

AVF3483s

Responsible Party

Sponsor

Study Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

 Genentech, Inc.

Study Sponsor

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

Verification Date

November 2011