Brief Title
Pemetrexed Plus Gemcitabine or Carboplatin for Patients With Advanced Malignant Pleural Mesothelioma
Official Title
Pemetrexed Plus Gemcitabine Or Carboplatin In Patients With Advanced Malignant Mesothelioma: A Randomized Phase II Trial
Brief Summary
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.
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Best Overall Response by RECIST Criteria (Version 1.0)
Secondary Outcome
Overall Survival
Condition
Mesothelioma
Intervention
pemetrexed disodium
Study Arms / Comparison Groups
Pemetrexed/Carboplatin
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
32
Start Date
November 2005
Completion Date
May 2011
Primary Completion Date
September 2009
Eligibility 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)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Nasser H. Hanna, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00101283
Organization ID
CDR0000401795
Secondary IDs
U10CA021115
Responsible Party
Sponsor
Study Sponsor
Eastern Cooperative Oncology Group
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Nasser H. Hanna, MD, Study Chair, Indiana University Melvin and Bren Simon Cancer Center
Verification Date
November 2012