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

This study has been terminated.
(Slow Accrual)
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00604461
First received: January 17, 2008
Last updated: November 21, 2013
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Mesothelioma
Drug: Carboplatin, Bevacizumab and Pemetrexed
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM)

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants With Partial Response (PR) of Target Lesions [ Time Frame: Up to 12 Months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Months of Progression Free Survival (PFS) [ Time Frame: 2 Years, 9 Months ] [ Designated as safety issue: No ]
    The PFS is defined as the duration of time from the start of treatment to time of progression or death, whichever occurs first.


Enrollment: 13
Study Start Date: October 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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™)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00604461

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Genentech, Inc.
Investigators
Principal Investigator: Tawee Tanvetyanon, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00604461     History of Changes
Other Study ID Numbers: MCC-14896, AVF3483s
Study First Received: January 17, 2008
Results First Received: November 17, 2011
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Carboplatin
Bevacizumab
Avastin
Pemetrexed
Alimta

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Bevacizumab
Carboplatin
Pemetrexed
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014