Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Unresectable or Metastatic Malignant Mesothelioma
Cisplatin is used to treat different cancers, including testicular, germ cell, head and
neck, bladder, and lung cancer. This drug has an atom-containing platinum, which is designed
to poison cancer cells, causing them to die.
Pemetrexed is designed to block enzymes in the body that play a part in tumor growth.
Imatinib mesylate is a drug that blocks certain proteins that play a part in the development
of cancer. Imatinib mesylate has also been shown to increase the effect of chemotherapy in
Before you can start treatment on this study, you will have what are called "screening
tests." These tests will help the doctor decide if you are eligible to take part in this
study. You will have your complete medical history recorded and a physical exam, including
measurement of your vital signs (temperature, pulse, breathing rate, and blood pressure) and
weight. An ECOG performance status evaluation (a test looking at your ability to perform
day-to-day activities) will be done. Blood will be drawn (about 3 to 4 teaspoons) through a
needle in your vein for routine tests. You will be asked about any medications you are
taking. Women who are able to have children must have a negative blood pregnancy test.
Also, your tumor will be evaluated by magnetic resonance imaging (MRI) or computerized
tomography (CT) scans before the start of this study.
If you are found to be eligible to take part in this study, you will begin taking imatinib
mesylate. Depending on when you begin treatment on this study, you may be asked to take 3,
4, or 6 tablets of imatinib mesylate by mouth once a day. Your doctor will also ask you to
take folic acid tablets (or a multivitamin with folic acid) during the week before you
receive your first infusion of pemetrexed and then every day while you are on this study.
You will also be given an injection of vitamin B12. The vitamin B12 shot will be repeated
every 9 weeks during treatment on this study. Folic acid and vitamin B12 will help to
decrease the risk of severe side effects from pemetrexed.
After 1 week of imatinib mesylate and folic acid, you will receive cisplatin and pemetrexed
by IV infusion. Cisplatin (given over 2 hours) and pemetrexed (given over 40 minutes) will
be given on the first day of each treatment cycle for a total of 6 cycles. Each cycle is 28
Dexamethasone will also be given by vein before you receive pemetrexed. Dexamethasone will
help to decrease the risk of rash and nausea that may be caused by pemetrexed. Your doctor
will also ask you to take dexamethasone tablets by mouth twice a day (12 hours apart) only
on Day 2 of each cycle.
Every 4 weeks, you will have a physical exam, including measurement of your vital signs and
weight. You will also have a performance status evaluation. Blood will be drawn (about 3
to 4 teaspoons) through a needle in your vein for routine tests. Also, at every 8 weeks,
your tumor will be measured by a CT or an MRI scan.
After you complete 6 treatment cycles of cisplatin and pemetrexed, you will continue to take
imatinib mesylate tablets every day up to 1 month after the 6 treatment cycles. If you
develop any intolerable side effects or if your disease gets worse, your treatment on this
study may be delayed; the dose of the study drugs decreased until your side effects are
gone; or you may be taken completely off this study. Your doctor will talk with you about
any changes in your dosing schedule or in the doses of your medication after you been
evaluated in the clinic.
After you have completed all of your treatment, you will have what is called an end-of-study
visit. At this visit, you will have a physical exam, including measurement of your vital
signs and weight. You will have an ECOG performance status evaluation. You will have blood
drawn (about 3 to 4 teaspoons) through a needed in your vein for routine tests. You will
also have your tumor measured by CT or an MRI scan.
This is an investigational study. Both cisplatin and pemetrexed have been approved by the
FDA for the treatment of malignant mesothelioma. The FDA has approved imatinib mesylate for
the treatment of leukemia and certain sarcomas; however, it has been authorized by the FDA
for use in research only in the treatment of malignant mesothelioma. Up to 42 patients will
take part in this study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Highest tolerable dose of drug combination (cisplatin, pemetrexed [Alimta®], and imatinib mesylate [Gleevec®]) that can be given to patients with unresectable or metastatic malignant mesothelioma.
Anne S. Tsao, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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