Cisplatin, Pemetrexed, and Imatinib Mesylate in Malignant Mesothelioma

NCT00402766 | Completed Phase 1

• 2 other identifiers: 2005-0288NCI-2012-01381
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Mesothelioma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Cisplatin, Pemetrexed, and Imatinib Mesylate Given to Participants with Unresectable or Metastatic Malignant Mesothelioma

  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).

  After six cycles of 28 day cycles, up 6 months

Study Arms (1)

Cisplatin + Imatinib + Pemetrexed

EXPERIMENTAL

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; Drug: Imatinib Mesylate; Drug: Pemetrexed; Drug: Dexamethasone

Interventions

Cisplatin DRUG

Starting Dose: 60 mg/m\^2 by vein, Over 2 Hours

Also known as: Platinol®-AQ, Platinol®, CDDP

Cisplatin + Imatinib + Pemetrexed

Imatinib Mesylate DRUG

Starting Dose: 300 mg PO Daily

Also known as: Gleevec, Imatinib, STI571, NSC-716051

Cisplatin + Imatinib + Pemetrexed

Pemetrexed DRUG

Starting Dose: 500 mg/m\^2 by vein, Over 40 Minutes

Also known as: Alimta, LY231514, MTA, Multitargeted Antifolate, NSC-698037

Cisplatin + Imatinib + Pemetrexed

Dexamethasone DRUG

20 mg by vein given prior to Pemetrexed therapy and 4 mg given orally on Day 2 of each cycle.

Also known as: Decadron

Cisplatin + Imatinib + Pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) 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.
• 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).

You may not qualify if:

• 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 failure)
• 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 infection).
• 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 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Mesothelioma; Mesothelioma, Malignant

Interventions

Cisplatin; Imatinib Mesylate; Pemetrexed; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Anne S. Tsao, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2006
• First Posted: November 22, 2006
• Study Start: August 1, 2006
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: November 18, 2015

Record last verified: 2015-11

Locations

US (1)