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Sponsors and Collaborators: |
Duke University Bristol-Myers Squibb |
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Information provided by: | Duke University |
ClinicalTrials.gov Identifier: | NCT00734864 |
The primary objective of this study is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of dasatinib when combined with protracted, daily temozolomide (TMZ). Secondary objectives are: To further evaluate the safety and tolerability of dasatinib plus protracted, daily TMZ; 2. To evaluate the pharmacokinetics of dasatinib when administered with protracted, daily TMZ among recurrent malignant glioma patients who are on and not on CYP-3A enzyme inducing anti-epileptic drugs (EIAEDs); 3. To evaluate for anti-tumor activity with this regimen in this patient population.
Condition | Intervention | Phase |
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Glioblastoma Multiforme Gliosarcoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Glioma |
Other: enzyme-inducing anti-epileptic drugs |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Phase I Study of Dasatinib Plus Protracted Temozolomide in Recurrent Malignant Glioma |
Estimated Enrollment: | 48 |
Study Start Date: | June 2009 |
Estimated Study Completion Date: | June 2012 |
Estimated Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1
Subjects taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs).
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Other: enzyme-inducing anti-epileptic drugs
Subjects taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs Phenytoin/Dilantin, Fosphenytoin/Cerebyx, Phenobarbital, Primidone/Mysoline, Oxcarbazepine/Trileptal, Carbamazepine/Tegretol).
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2
Subjects NOT taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs).
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Other: enzyme-inducing anti-epileptic drugs
Subjects NOT taking EIAEDs (CYP-3A enzyme-inducing anti-epileptic drugs Phenytoin/Dilantin, Fosphenytoin/Cerebyx, Phenobarbital, Primidone/Mysoline, Oxcarbazepine/Trileptal, Carbamazepine/Tegretol).
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This is an open-label, single center, one-arm phase I dose-escalation study of dasatinib plus protracted , daily TMZ administered orally on a continuous daily dosing schedule among adult patients with recurrent or relapsing malignant glioma. The study format includes a classical "3+3" dose escalation design to determine the MTD and DLT of dasatinib plus protracted, daily TMZ among recurrent malignant glioma patients. Patients will be stratified based on whether they are receiving EIAED and each stratum will independently dose escalate. Additionally, the study will characterize the safety, tolerability, biologic activity, and pharmacokinetic profile of dasatinib when used in combination with protracted, daily TMZ.
Patients will start treatment on day 1 of cycle 1 with dasatinib. For patients undergoing dasatinib pharmacokinetic (PK) analysis, dasatinib will be administered alone until initial PK assessments are collected. Protracted TMZ will be initiated after initial dasatinib PK assessments are collected and will continue to be administered with dasatinib on a continuous daily dosing schedule. The initial dasatinib PK assessments will be collected over 24 hours between days 3-7 of cycle 1. Patients not undergoing dasatinib PK collections will begin both dasatinib and protracted, daily TMZ together on day 1, cycle 1.
The protracted, daily TMZ dose will be 50 mg/m² daily for all patients. The dose level of dasatinib will be increased in successive cohorts. Cohorts of 3-6 patients will accrue at each dose level until MTD is defined. Each cohort will consist of a minimum of 3 newly enrolled patients. Intra-patient dose escalation is not permitted. It is estimated that this study will enroll a minimum of 30 patients (up to 4 dose levels/stratum; 3 patients/dose level for levels 1-3 and 6 patients at level 4) and a maximum of 48 patients (6 patients/dose level; 4 dose levels/stratum). Cohorts may be expanded at any dose level for further elaboration of safety and pharmacokinetic parameters as required.
The primary safety and efficacy analysis will be conducted on all patient data at the time all patients who are still receiving study drug will have completed at least 4 cycles of treatment. The additional data for any patients continuing to receive study drug past this time, as allowed by the protocol, will be further summarized in a report once these patients either completed or discontinued the study. Prior to the primary analysis, an additional safety report may be prepared.
The most common side effects include vomiting, diarrhea, anorexia (loss of appetite), fluid retention, fatigue, headache, rash, hypocalcemia (low calcium level), and decreases in blood counts. Other possible side effects may include nausea, joint pain, muscle aches, generalized pain, abdominal pain, and fever. Rare side effects may include QTc prolongation (heart beat changes), pulmonary edema (fluid around the lungs), difficulty breathing, cough, hemorrhage, gastrointestinal bleeding, pneumonia, cardiac effusion (fluid in the sac surrounding the heart), and cardiac failure. Temodar has been well tolerated by both adults and children with the most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, hepatotoxicity, anorexia, fatigue and hyperglycemia. As in the case with many anti-cancer drugs, Temodar may be carcinogenic. Rats given Temodar have developed breast cancer.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Significant cardiac disease including any of the following:
Concomitant Medications, consider the following prohibitions:
Drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)
Contact: Annick Desjardins, MD | 919-681-1691 | desja002@mc.duke.edu |
Contact: Stevie Threatt | (919) 684-3657 | threa003@mc.duke.edu |
United States, North Carolina | |
Duke University Medical Center | |
Durham, North Carolina, United States, 27710 |
Principal Investigator: | Annick Desjardins, MD | Duke University |
Responsible Party: | Duke University Medical Center ( Annick Desjardins, MD ) |
Study ID Numbers: | 00007909, BMS Protocol #CA180-108 |
Study First Received: | May 4, 2008 |
Last Updated: | December 26, 2008 |
ClinicalTrials.gov Identifier: | NCT00734864 |
Health Authority: | United States: Food and Drug Administration; United States: Institutional Review Board |
gliosarcoma Dasatinib Sprycel Temozolomide Temodar Recurrent Malignant Glioma |
Malignant Glioma glioblastoma multiforme anaplastic astrocytoma anaplastic oligodendroglioma anaplastic mixed glioma glioma |
Glioblastoma Phenobarbital Primidone Oxcarbazepine Astrocytoma Temozolomide Fosphenytoin Recurrence Phenytoin Neuroectodermal Tumors |
Carbamazepine Glioblastoma multiforme Dasatinib Neoplasms, Germ Cell and Embryonal Neuroepithelioma Oligodendroglioma Glioma Gliosarcoma Neoplasms, Glandular and Epithelial |
Neoplasms Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Therapeutic Uses Neoplasms, Nerve Tissue |
Enzyme Inhibitors Antineoplastic Agents, Alkylating Neoplasms, Neuroepithelial Protein Kinase Inhibitors Alkylating Agents Pharmacologic Actions |