Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Unresectable or Metastatic Malignant Mesothelioma
18 Years
N/A
Both
Mesothelioma
Trial Information
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
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.
Inclusion Criteria:
1. A written, voluntary informed consent form must be completed prior to beginning any
study procedure.
2. Patients >/= 18 years of age.
3. Histologically documented diagnosis of malignant mesothelioma.
4. Performance status 0-2 (ECOG)
5. Patients must have adequate hepatic,renal,& bone marrow function,defined as the
following:(1) total bilirubin 1.5xULN;(4) ANC >/= 1.5x10^9/L;(5) platelets>/=100 x 10^9/L.Note:Renal function is
only based on serum creatinine level formula or the measured glomerular filtration rate (GFR) using the appropriate radio
labelled method (51-CrEDTA or Tc99m-DTPA) must be used to calculate CrCl for
enrollment or dosing.The same method used @ baseline should be used throughout the
study.CrCl should be >/= 45mg/dl.
6. Female patients of childbearing potential must have negative pregnancy test within 7
days before initiation of study drug dosing. Postmenopausal women must be amenorrheic
for at least 12 months to be considered of non-childbearing potential. Male and
female patients of reproductive potential must agree to employ an effective barrier
method of birth control throughout the study and for up to 3 months following
discontinuation of study drug.
7. Patients who have not received prior chemotherapy for their metastatic or recurrent
unresectable malignant mesothelioma; with the exception of patients who have
recurrent mesothelioma after induction chemotherapy followed by definitive treatment
(surgery +/- radiotherapy). Patients must have had 2 or fewer cycles/doses of
induction chemotherapy and must have had tumor response to the induction therapy.
8. Patients must have documented unresectable malignant mesothelioma (pleural or
peritoneal).
9. Patients with treated brain metastasis who have stable brain disease (i.e. no
steroids at least 4 weeks prior to study enrollment).
Exclusion Criteria:
1. Patient has received any other investigational agents within 28 days of first day of
study drug dosing.
2. Patient is primary malignancy is not currently clinically significant nor requiring active
intervention, or if other primary malignancy is a basal cell skin cancer, squamous
skin cancer, or a cervical carcinoma in situ.
3. Patient with Grade III/IV cardiac problems as defined by the New York Heart
Association Criteria. (i.e., congestive heart failure)
4. Patients with myocardial infarction within 6 months of study.
5. Female patients who are pregnant or breast-feeding.
6. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled
diabetes, chronic renal disease, or active uncontrolled infection).
7. Patient has a known untreated or unstable brain metastasis.
8. Patient has known chronic liver disease (i.e., chronic active hepatitis, and
cirrhosis).
9. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection. HIV
patients are at much greater risk of infection when receiving highly myelosuppressive
agents (cisplatin, pemetrexed, and imatinib) and for safety reasons are not eligible
for this trial.
10. Patient who received prior chemotherapy for their malignant mesothelioma with the
exception listed in inclusion criteria #7.
11. Patient previously received radiotherapy to >/= 25 % of the bone marrow.
12. Patient had a major surgery within 2 weeks prior to study entry.
13. Patient with any significant history of non-compliance to medical regimens or with
inability to grant reliable informed consent.
14. Patients must agree not to use herbal remedies or other over-the-counter biologics
(i.e. shark cartilage).
15. Prior exposure to imatinib mesylate.
16. Patients taking therapeutic levels of warfarin. However, patients receiving 1 mg
daily for catheter related anticoagulation are eligible for the study.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
4 Years
Safety Issue:
Yes
Principal Investigator
Anne S. Tsao, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2005-0288
NCT ID:
NCT00402766
Start Date:
August 2006
Completion Date:
Related Keywords:
- Mesothelioma
- Mesothelioma
- Pleural Mesothelioma
- Peritoneal Mesothelioma
- PDGF-R
- Pemetrexed
- Alimta
- Cisplatin
- Imatinib Mesylate
- Gleevec
- Platinol
- Platinol-AQ
- CDDP
- Ly231514
- Multitargeted Antifolate
- NSC-698037
- STI571
- NSSC-716051
- Mesothelioma
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
