Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM)
Primary Purpose
Mesothelioma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carboplatin, Bevacizumab and Pemetrexed
Sponsored by
About this trial
This is an interventional treatment trial for Mesothelioma focused on measuring Carboplatin, Bevacizumab, Avastin, Pemetrexed, Alimta
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.
Sites / Locations
- H. Lee Moffitt Cancer Center & Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose Escalation Followed by Maintenance Therapy
Arm 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of Months of Progression Free Survival (PFS)
The PFS is defined as the duration of time from the start of treatment to time of progression or death, whichever occurs first.
Full Information
NCT ID
NCT00604461
First Posted
January 17, 2008
Last Updated
February 20, 2017
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00604461
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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2011
Overall Recruitment Status
Terminated
Why Stopped
Slow Accrual
Study Start Date
October 2007 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Genentech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesothelioma
Keywords
Carboplatin, Bevacizumab, Avastin, Pemetrexed, Alimta
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation Followed by Maintenance Therapy
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin, Bevacizumab and Pemetrexed
Other Intervention Name(s)
Bevacizumab (Avastin™), Pemetrexed (Alimta™)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Partial Response (PR) of Target Lesions
Description
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.
Time Frame
Up to 12 Months
Secondary Outcome Measure Information:
Title
Number of Months of Progression Free Survival (PFS)
Description
The PFS is defined as the duration of time from the start of treatment to time of progression or death, whichever occurs first.
Time Frame
2 Years, 9 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tawee Tanvetyanon, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM)
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