Pemetrexed Plus Gemcitabine or Carboplatin for Patients With Advanced Malignant Pleural Mesothelioma - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborators:	National Cancer Institute (NCI) North Central Cancer Treatment Group
Information provided by:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00101283

Purpose

RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, gemcitabine, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether giving pemetrexed disodium with gemcitabine is more effective than giving pemetrexed disodium with carboplatin in treating malignant pleural mesothelioma.

PURPOSE: This randomized phase II trial is studying pemetrexed disodium with gemcitabine and pemetrexed disodium with carboplatin to see how well the combinations work compared to historical controls in treating patients with advanced malignant pleural mesothelioma.

Condition	Intervention	Phase
Mesothelioma	Drug: pemetrexed disodium Drug: gemcitabine hydrochloride Drug: carboplatin	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pemetrexed Plus Gemcitabine Or Carboplatin In Patients With Advanced Malignant Mesothelioma: A Randomized Phase II Trial

Resource links provided by NLM:

MedlinePlus related topics: Cancer Mesothelioma

Drug Information available for: Carboplatin Gemcitabine Gemcitabine hydrochloride Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:

Best Overall Response by RECIST Criteria (Version 1.0) [ Time Frame: Assessed every 2 cycles (6 weeks) while on treatment, then every 3 months for 2 years, then every 6 months for 1 year until disease progression ] [ Designated as safety issue: No ]
Number of eligible, treated participants in each response category by RECIST criteria. Response categories represent best response for each patient prior to progression.

Secondary Outcome Measures:

Overall Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 1 year ] [ Designated as safety issue: No ]
Time from randomization to death. Patients alive at last follow-up were censored.
Progression-Free Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 1 year ] [ Designated as safety issue: No ]
Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.

Enrollment:	32
Study Start Date:	November 2005
Estimated Study Completion Date:	July 2010
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pemetrexed/Carboplatin Pemetrexed disodium 500 mg/m2 IV over 10 minutes and carboplatin to area under the curve (AUC) 5 IV over 30 minutes on day 1 of a 21-day cycle.	Drug: pemetrexed disodium 500 mg/m2 IV over 10 minutes on day 1 of a 21-day cycle Other Names: Alimta MTA LY231514 Drug: carboplatin Given by IV over 30 minutes at an area under the curve (AUC) of 5 on day 1 of a 21-day cycle Other Names: CBDCA Paraplatin JM-8 NSC-241240
Experimental: Pemetrexed/Gemcitabine Pemetrexed disodium 500 mg/m2 IV over 10 minutes on day 1 and gemcitabine 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21-day cycle.	Drug: pemetrexed disodium 500 mg/m2 IV over 10 minutes on day 1 of a 21-day cycle Other Names: Alimta MTA LY231514 Drug: gemcitabine hydrochloride 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21-day cycle Other Name: Gemzar

Detailed Description:

OBJECTIVES:

Primary

Estimate the response rates in patients with advanced malignant mesothelioma of the pleura treated with pemetrexed disodium combined with either gemcitabine or carboplatin.

Secondary

Assess the toxic effects of these regimens in these patients.
Estimate survival time in patients treated with these regimens.
Correlate smoking status with outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. While randomized, the study is not a comparative study. Rather, outcomes on each arm will be compared to a historical control rate from previous studies. Randomization allows simultaneous testing of two experimental arms.

Arm I: Patients receive intravenous (IV) pemetrexed disodium over 10 minutes and carboplatin IV over 30 minutes on day 1.
Arm II: Patients receive pemetrexed disodium as in arm I and gemcitabine IV over 30 minutes on days 1 and 8.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Beginning approximately 5-10 days before the start of chemotherapy and continuing until approximately 3 weeks after completion of chemotherapy, all patients receive oral folic acid once daily and cyanocobalamin (vitamin B12) intramuscularly every 9 weeks.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 32-60 patients (16-30 per treatment arm) will be accrued for this study within 12.8-27.0 months.

Eligibility

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

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed advanced mesothelioma of the pleura
Measurable disease, as defined by RECIST criteria, within 4 weeks of randomization. Patients with pleural rinds not measurable by RECIST were eligible if disease was evaluable within 4 weeks of randomization using mesothelioma response criteria
May have undergone pleurodesis. If pleurodesis was performed, there must have been at least a 2-week delay before Pemetrexed administration. A CT must have been performed after 2 weeks after pleurodesis to serve as the baseline scan.
ECOG Performance Status of 0 or 1
Normal organ and marrow function, as defined by:
- Absolute neutrophil count ≥ 1,500/ul
- Platelet count ≥ 100,000/ul
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement)
- Albumin ≥ 2.5 g/dL
- Creatinine clearance ≥ 45 mL/min or Creatinine ≤ 2.0 g/dL
Age 18 years and over
Able to take folic acid and cyanocobalamin (vitamin B12)
Willing and able to take dexamethasone
Women of childbearing potential and sexually active men were required to use contraception during and for the first 3 months after the study

Exclusion Criteria

A candidate for curative surgery
Prior radiation therapy to the target lesion, unless the lesion was clearly progressing per RECIST criteria after prior radiation and the interval between the most recent radiation therapy and enrollment was at least 4 weeks
Prior systemic chemotherapy for mesothelioma. Prior intracavitary cytotoxic drugs or immunomodulators were not permitted, unless given for the purpose of pleurodesis.
Active infection or serious concomitant systemic disorder
Second primary malignancy, other than in situ malignancies or adequately treated basal cell carcinoma of the skin or other malignancy treated at least 3 years previously with no evidence of recurrence.
Treatment with an investigational agent within 4 weeks before enrollment
Known or suspected brain metastases
Women must not be pregnant or breastfeeding
Obviously malnourished or with a weight loss of greater than 10% in the preceding 6 weeks
Aspirin or other nonsteroidal anti-inflammatory drugs for 2 days before, during, and for 2 days after each administration of pemetrexed disodium (5 days before, during, and 2 days after each administration of pemetrexed disodium for piroxicam, naproxen, diflunisal, or nabumetone)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00101283

Show 115 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

North Central Cancer Treatment Group

Investigators

Study Chair:	Nasser H. Hanna, MD	Indiana University Melvin and Bren Simon Cancer Center
Study Chair:	Scott Okuno, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00101283 History of Changes
Other Study ID Numbers:	CDR0000401795, U10CA021115, E1B03, E1B03
Study First Received:	January 7, 2005
Results First Received:	February 12, 2010
Last Updated:	March 23, 2010
Health Authority:	United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:

advanced malignant mesothelioma
recurrent malignant mesothelioma

Additional relevant MeSH terms:

Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Gemcitabine
Pemetrexed
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Folic Acid Antagonists

ClinicalTrials.gov processed this record on February 09, 2012