Official Title: Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Unresectable or Metastatic Malignant Mesothelioma
Further study details as provided by M.D. Anderson Cancer Center:
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 2 weeks while you are on this study, you will have a physical exam, including measurement of your vital signs and weight.
An ECOG performance status evaluation will be done. 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. Imatinib mesylate will be provided
to you free of charge during this study. Cisplatin and pemetrexed will not be provided free of charge during this study and
will be billed to you or your insurance company. Up to 42 patients will take part in this study. All will be enrolled at
M. D. Anderson.
Ages Eligible for Study:
18 Years and above,
Genders Eligible for Study:
- A written, voluntary informed consent form must be completed prior to beginning any study procedure.
- Patients >/= 18 years of age.
- Histologically documented diagnosis of malignant mesothelioma.
- Performance status 0-2 (ECOG)
- Patients must have adequate hepatic,renal,& bone marrow function,defined as the following:(1) total bilirubin </=1.5xULN;(2)
SGOT & SGPT</=2.5xULN;(3)creatinine </= 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 </= 1.5xULN.The standard Cockcroft & Gault formula or the measured glomerular filtration
rate (GFR) using the appropriate radiolabelled 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.
- 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.
- 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.
- Patients must have documented unresectable malignant mesothelioma (pleural or peritoneal).
- Patients with treated brain metastasis who have stable brain disease (i.e. no steroids at least 4 weeks prior to study enrollment).
- Patient has received any other investigational agents within 28 days of first day of study drug dosing.
- Patient is </= 5 years free of another primary malignancy except: if the other 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.
- Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart
- Patients with myocardial infarction within 6 months of study.
- Female patients who are pregnant or breast-feeding.
- Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled
- Patient has a known untreated or unstable brain metastasis.
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
- 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.
- Patient who received prior chemotherapy for their malignant mesothelioma with the exception listed in inclusion criteria #7.
- Patient previously received radiotherapy to >/= 25 % of the bone marrow.
- Patient had a major surgery within 2 weeks prior to study entry.
- Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- Patients must agree not to use herbal remedies or other over-the-counter biologics (i.e. shark cartilage).
- Prior exposure to imatinib mesylate.
- Patients taking therapeutic levels of warfarin. However, patients receiving 1 mg daily for catheter related anticoagulation
are eligible for the study.
Please refer to this study by ClinicalTrials.gov identifier
Anne S. Tsao, MD
U.T.M.D. Anderson Cancer Center, Houston,
United States; Recruiting
Anne S. Tsao, MD, Principal Investigator
Study chairs or principal investigators
Anne S. Tsao, MD, Principal Investigator, U.T.M.D. Anderson Cancer Center
Study ID Numbers:
November 20, 2006
Record first received:
November 20, 2006
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-11-28