Cisplatin, Pemetrexed, and Imatinib Mesylate in Malignant Mesothelioma

Mesothelioma Clinical Trial

Official title: Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Unresectable or Metastatic Malignant Mesothelioma

Status Completed

Clinical Trial Summary

Primary Objective:

• To determine the maximum tolerated dose of the combination of cisplatin, imatinib mesylate, and pemetrexed in metastatic malignant mesothelioma.

Secondary Objectives:

• To explore the biologic effects of cisplatin, imatinib mesylate, and pemetrexed on tumor tissue by:

• histologic analysis of biopsy tissue

• by non-invasive assessments of tumor vascularity performed before, during and after treatment

• electron microscopy analysis of endothelial cell architecture after patient treatment with imatinib mesylate

• To explore the effects of cisplatin, imatinib mesylate, and pemetrexed on surrogate markers in serum.

• To assess the rate of response to therapy.

• To determine the doses of the combination regimen of cisplatin, imatinib mesylate, and pemetrexed that enables de-phosphorylation of platelet derived growth factor receptor (PDGF-R) on malignant mesothelioma tumor cells.

• To determine the pharmacokinetic interaction between agents in this combination regimen.

Clinical Trial Description

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 tumor cells.

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 days long.

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. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Mesothelioma

• NCT number: NCT00402766
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: August 2006
• Completion date: February 2014