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Cisplatin, Pemetrexed, and Imatinib Mesylate in Malignant Mesothelioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00402766
Recruitment Status : Completed
First Posted : November 22, 2006
Last Update Posted : November 18, 2015
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Mesothelioma Drug: Cisplatin Drug: Imatinib Mesylate Drug: Pemetrexed Drug: Dexamethasone Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Unresectable or Metastatic Malignant Mesothelioma
Study Start Date : August 2006
Actual Primary Completion Date : February 2014
Actual Study Completion Date : February 2014

Arm Intervention/treatment
Experimental: Cisplatin + Imatinib + Pemetrexed
Cisplatin 60 mg/m^2 by vein, Over 2 Hours. Imatinib 300 mg PO Daily. Pemetrexed 500 mg/m^2 by vein, Over 40 Minutes. Dexamethasone 20 mg by vein given prior to Pemetrexed therapy and 4 mg given orally on Day 2 of each cycle.
Drug: Cisplatin
Starting Dose: 60 mg/m^2 by vein, Over 2 Hours
Other Names:
  • Platinol®-AQ
  • Platinol®
  • CDDP

Drug: Imatinib Mesylate
Starting Dose: 300 mg PO Daily
Other Names:
  • Gleevec
  • Imatinib
  • STI571
  • NSC-716051

Drug: Pemetrexed
Starting Dose: 500 mg/m^2 by vein, Over 40 Minutes
Other Names:
  • Alimta
  • LY231514
  • MTA
  • Multitargeted Antifolate
  • NSC-698037

Drug: Dexamethasone
20 mg by vein given prior to Pemetrexed therapy and 4 mg given orally on Day 2 of each cycle.
Other Name: Decadron

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Cisplatin, Pemetrexed, and Imatinib Mesylate Given to Participants with Unresectable or Metastatic Malignant Mesothelioma [ Time Frame: After six cycles of 28 day cycles, up 6 months ]
    MTD defined as the highest dose level in which 6 patients have been treated with less than or equal to 2 instances of dose limiting toxicity (DLT). DLT characterized by the National Cancer Institute (NCI) Common Toxicity Criteria. DLT defined as (1) febrile neutropenia (fever > grade 2 with grade 4 neutropenia and requiring IV antibiotics); (2) grade 4 neutropenia (ANC < 500/mL) for more than seven days duration; (3) grade 4 thrombocytopenia; (4) grade 3 or 4 non-hematologic toxicity (except alopecia).

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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;(2) serum glutamate oxaloacetate transaminase (SGOT) & serum glutamate pyruvate transaminase (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 radio labelled method (51-CrEDTA or Tc99m-DTPA) must be used to calculate cranial cruciate ligament (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 </= 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00402766

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
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Principal Investigator: Anne S. Tsao, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00402766    
Other Study ID Numbers: 2005-0288
NCI-2012-01381 ( Registry Identifier: NCI CTRP )
First Posted: November 22, 2006    Key Record Dates
Last Update Posted: November 18, 2015
Last Verified: November 2015
Keywords provided by M.D. Anderson Cancer Center:
Pleural Mesothelioma
Peritoneal Mesothelioma
Imatinib Mesylate
Multitargeted Antifolate
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Imatinib Mesylate
Antineoplastic Agents
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors