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

NCT00604461 | Terminated Phase 1 Results DMC

• 2 other identifiers: MCC-14896AVF3483s
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Mesothelioma

Keywords

Carboplatin; Bevacizumab; Avastin; Pemetrexed; Alimta

Outcome Measures

Primary Outcomes (1)

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

  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 Outcomes (1)

• Number of Months of Progression Free Survival (PFS)

  2 Years, 9 Months

Study Arms (1)

Dose Escalation Followed by Maintenance Therapy

EXPERIMENTAL

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

Interventions

Carboplatin, Bevacizumab and Pemetrexed DRUG

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.

Also known as: Bevacizumab (Avastin™), Pemetrexed (Alimta™)

Dose Escalation Followed by Maintenance Therapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Genentech, Inc.: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Mesothelioma

Interventions

Carboplatin; Bevacizumab; Pemetrexed

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Limitations and Caveats

This trial was closed early due to slow patient accrual. The planned accrual had been 44.

Results Point of Contact

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

tawee.tanvetyanon@moffitt.org

813-745-3050

Study Officials

• Tawee Tanvetyanon, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 30, 2008
• Study Start: October 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: March 23, 2017
• Results First Posted: December 26, 2011

Record last verified: 2011-11

Locations

US (1)