Pemetrexed Plus Gemcitabine or Carboplatin for Patients With Advanced Malignant Pleural Mesothelioma
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|ClinicalTrials.gov Identifier: NCT00101283|
Recruitment Status : Completed
First Posted : January 10, 2005
Results First Posted : March 4, 2010
Last Update Posted : December 4, 2012
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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 or disease||Intervention/treatment||Phase|
|Mesothelioma||Drug: pemetrexed disodium Drug: gemcitabine hydrochloride Drug: carboplatin||Phase 2|
- Estimate the response rates in patients with advanced malignant mesothelioma of the pleura treated with pemetrexed disodium combined with either gemcitabine or carboplatin.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pemetrexed Plus Gemcitabine Or Carboplatin In Patients With Advanced Malignant Mesothelioma: A Randomized Phase II Trial|
|Study Start Date :||November 2005|
|Actual Primary Completion Date :||September 2009|
|Actual Study Completion Date :||May 2011|
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
Given by IV over 30 minutes at an area under the curve (AUC) of 5 on day 1 of a 21-day cycle
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
Drug: gemcitabine hydrochloride
1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21-day cycle
Other Name: Gemzar
- 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 ]Number of eligible, treated participants in each response category by RECIST criteria. Response categories represent best response for each patient prior to progression.
- Overall Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 1 year ]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 ]Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00101283
|Study Chair:||Nasser H. Hanna, MD||Indiana University Melvin and Bren Simon Cancer Center|
|Study Chair:||Scott Okuno, MD||Mayo Clinic|
|Responsible Party:||Eastern Cooperative Oncology Group|
|Other Study ID Numbers:||
U10CA021115 ( U.S. NIH Grant/Contract )
E1B03 ( Other Identifier: ECOG )
E1B03 ( Other Identifier: NCCTG )
|First Posted:||January 10, 2005 Key Record Dates|
|Results First Posted:||March 4, 2010|
|Last Update Posted:||December 4, 2012|
|Last Verified:||November 2012|
advanced malignant mesothelioma
recurrent malignant mesothelioma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors