Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With MPM - Full Text View

Sponsors and Collaborators:	H. Lee Moffitt Cancer Center and Research Institute Genentech
Information provided by:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00604461

Purpose

The purpose of this research study is 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.

Primary:

Determine the Overall Survival (OS), (median survival(MS) and 1-yr survival (1-yr S)), in newly diagnosed patients with MPM who are treated with a regimen consisting of cisplatin, bevacizumab, and pemetrexed. Patients will be followed until death and survival curves will be generated. Response rates will be assessed.

Secondary:

Estimate the progression free survival (PFS)
Determine the response rates
Safety of the regimen will also be assessed.

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

Condition	Intervention	Phase
Mesothelioma	Drug: Carboplatin, Bevacizumab and Pemetrexed	Phase I Phase II

MedlinePlus related topics: Cancer Mesothelioma

Drug Information available for: Carboplatin Pemetrexed disodium Pemetrexed Bevacizumab

U.S. FDA Resources

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

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

Primary Outcome Measures:

Determine if Overall Survival (OS) in newly diagnosed patients with MPM who are treated first-line with a regimen consisting of carboplatin, bevacizumab, and pemetrexed exceeds 12 months. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Estimate the progression free survival (PFS). Determine the response rates. Safety of the regimen will also be assessed. [ Time Frame: Patient will be taken off the study at the time of progression. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	48
Study Start Date:	October 2007
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A, B: Experimental A: Tiered Dose Escalation/Phase II Dose, B: Maintenance Therapy	Drug: Carboplatin, Bevacizumab and Pemetrexed Tier -1: Carboplatin AUC 4 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m2 Tier 1: Carboplatin AUC 5 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m2 Tier 2: Carboplatin AUC 6 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m2 Chemotherapy will be given for two cycles after maximal response. Patients will be taken off study at the time of progression. If the patient has stable disease or better, as a response, then patient will be maintained on pemetrexed plus bevacizumab for a total of one year after initiation of maintenance or until progression which ever occurs first. CT scans will be done every 12 weeks during maintenance phase

Arms

Assigned Interventions

A, B: Experimental

A: Tiered Dose Escalation/Phase II Dose,

B: Maintenance Therapy

Drug: Carboplatin, Bevacizumab and Pemetrexed

Tier -1: Carboplatin AUC 4 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m2

Tier 1: Carboplatin AUC 5 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m2

Tier 2: Carboplatin AUC 6 + Bevacizumab 15 mg/Kg+Pemetrexed 500 mg/m2

Chemotherapy will be given for two cycles after maximal response. Patients will be taken off study at the time of progression. If the patient has stable disease or better, as a response, then patient will be maintained on pemetrexed plus bevacizumab for a total of one year after initiation of maintenance or until progression which ever occurs first. CT scans will be done every 12 weeks during maintenance phase

Detailed Description:

A blood sample will be taken to check the patient's blood and platelet counts before each Pemetrexed dose. Before each cycle, we will review the patient's medical history, give them a physical exam (including vital signs: blood pressure, heart rate, breathing rate, temperature), and check their weight, performance status and blood. The patient's tumor will be measured after every other cycle. The patient's urine will be tested before every other cycle with Bevacizumab.

Treatment Regimen: To ensure the safety, before initiating the phase II dose, we will have a brief phase I portion, where tiered dose escalation to the anticipated phase II dose will occur.

Tier I Carboplatin at AUC of 5 Bevacizumab 15 mg/Kg I.V. on day 1 Pemetrexed 500 mg/m2 on day 1 Every 21 days

Tier II (Target dose) Carboplatin at AUC of 6 Bevacizumab 15 mg/Kg I.V. on day 1 Pemetrexed 500 mg/m2 on day 1 Every 21 days

Tier (-1) Carboplatin at AUC of 4 Bevacizumab 15 mg/Kg I.V. on day 1 Pemetrexed 500 mg/m2 on day 1 Every 21 days

With each cycle, we will give the following:

Folic Acid 300 µg to 1 mg orally once daily starting day 1. B12 injections given subcutaneously any time between days -7 to 1 of the first cycle and then every 9 weeks.

Dexamethasone 4mb BID on day-1,0, and day +1

Patients will be enrolled in cohorts of three. If one of the three patients has a dose limiting toxicity (DLT) then three additional patients will be enrolled. If no DLTs occur then patients will be accrued in the next dose level. If two DLTs occur in a cohort of three patients or in an expanded cohort of 6 patients then that dose level will be called the Maximum Administered Dose (MAD). A dose level below will be called the MTD and will be the recommended dose for further phase II testing. Al three patients in a cohort must complete one full cycle, before proceeding to the next cohort.

DLT will be defined as grade 4 neutropenia, febrile neutropenia, and any grade 3 or 4 non-hematologic toxicity except for alopecia and nausea/vomiting/diarrhea without adequate prophylaxis. (CTC version 3.0).

No further dose escalation will be attempted beyond dose Tier 2. If there are no dose-limiting toxicities in dose Tier 2 then this will be considered the phase II dose. If there is a DLT in dose Tier 1 then we will enroll 3 patients in Tier -1 and if no further DLTs occur then Tier -1 will be the phase II dose.

When the patient goes off-study, they will have a physical exam, tumor measurements, and blood test evaluations.

Each study patient will be contacted every 3 months for the rest of their life. Information about any extra treatments they have received will be collected and recorded if they are taken off-study because their disease got worse. If they are taken off-study for any other reason, we will collect information on any extra anti-cancer treatments they have received for Malignant Pleural Mesothelioma (MPM).

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 ascities (symptomatic or detectable by clinical exam) should have their effusions drained prior to enrollment on the clinical trial.

Exclusion Criteria:

Patients with hypercalceamia (corrected calcium of more than 11 mg/dl) will be excluded.
Patients with history of hemoptysis, hemetemesis, 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. (Please see Appendix III.)
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. (Please see Appendix VI).
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00604461

Contacts

Contact: Melissa Joiner, R.N.

813-745-1896

melissa.joiner@moffitt.org

Locations

United States, Florida
H. Lee Moffitt Cancer Center & Research Institute	Recruiting
Tampa, Florida, United States, 33612
Principal Investigator: Roohi Ismail-Khan, M.D.
Principal Investigator: George Simon, M.D.
Sub-Investigator: Scott Antonia, M.D.
Sub-Investigator: Gerold Bepler, M.D.
Sub-Investigator: Alberto Chiappori, M.D.
Sub-Investigator: Lynn Coppage, M.D.
Sub-Investigator: Eric Haura, M.D.
Sub-Investigator: Todd Hazelton, M.D.
Sub-Investigator: Tawee Tanvetyanon, M.D.
Sub-Investigator: Charles Williams, M.D.

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Genentech

Investigators

Principal Investigator:	Roohi Ismail-Khan, M.D.	H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator:	George Simon, M.D.	H. Lee Moffitt Cancer Center & Research Institutute

More Information

Moffitt Cancer Center Clinical Trials website This link exits the ClinicalTrials.gov site

Responsible Party:	H. Lee Moffitt Cancer Center & Research Institute ( Roohi Ismail-Khan, M.D. )
Study ID Numbers:	MCC-14896, USFIRB#105715, AVF3483s
Study First Received:	January 17, 2008
Last Updated:	January 29, 2008
ClinicalTrials.gov Identifier:	NCT00604461
Health Authority:	United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Carboplatin
Bevacizumab
Avastin
Pemetrexed
Alimta

Study placed in the following topic categories:

Folic Acid
Pemetrexed
Mesothelioma
Carboplatin

Bevacizumab
Adenoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Neoplasms, Mesothelial
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs

Enzyme Inhibitors
Folic Acid Antagonists
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on January 14, 2009