Ph. I Dasatinib/Protracted Temozolomide in Recurrent Malignant Glioma

NCT00734864 | Withdrawn Phase 1

• 2 other identifiers: Pro00007909BMS Protocol #CA180-108
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma Multiforme; Gliosarcoma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Glioma

Keywords

Dasatinib; Sprycel; Temozolomide; Temodar; Recurrent Malignant Glioma; Malignant Glioma; glioblastoma multiforme; gliosarcoma; anaplastic astrocytoma; anaplastic oligodendroglioma; anaplastic mixed glioma; glioma

Outcome Measures

Primary Outcomes (1)

• Toxicity assessed using CTCAE v.3.0

  weekly

Secondary Outcomes (2)

• Progression free and overall survival

  continuous

• Radiographic response (modified MacDonald Criteria)

  every 28 days

Study Arms (2)

1

OTHER

Subjects taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs).

Drug: enzyme-inducing anti-epileptic drugs

2

OTHER

Subjects NOT taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs).

Drug: enzyme-inducing anti-epileptic drugs

Interventions

enzyme-inducing anti-epileptic drugs DRUG

Subjects taking EIAEDs (CYP3A enzyme-inducing anti-epileptic drugs Phenytoin/Dilantin, Fosphenytoin/Cerebyx, Phenobarbital, Primidone/Mysoline, Oxcarbazepine/Trileptal, Carbamazepine/Tegretol).

1

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically confirmed diagnosis of a recurrent/progressive WHO Gr.4 malignant glioma (glioblastoma multiforme or gliosarcoma) or WHO Gr.3 malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic mixed glioma). Recurrence will be defined based on the modified MacDonald criteria or based on histopathologic confirmation of tissue obtained via surgical intervention. Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO Gr.III or IV malignant glioma;
• \> or = to 18 y/o;
• KPS . or = to 60%;
• Patients must be presenting in 1st, 2nd or 3rd relapse. Relapse is defined as progression following anti-cancer therapy other than surgery, including non-surgical therapies that are considered standard treatment for high-grade glioma if administered to patients with prior low-grade glioma. Prior therapy must have included external beam radiotherapy;
• Adequate bone marrow, liver and renal function as assessed by the following: Hematocrit \> or = to 29%, ANC \> or = to 1,500/mm3, Platelet count \> or = to 125,000/mm3, Total bilirubin \< or = to 1.5 x ULN, ALT and AST \< or = to 2.5 x the ULN ( \< or = to 5 x ULN for patients with liver involvement), INR \< 1.5 or a PT/PTT within normal limits (unless on therapeutic anti-coagulation). Patients receiving anti-coagulation treatment with a low-molecular weight heparin will be allowed to participate, however oral warfarin is not permitted except for low-dose warfarin (1mg po DAILY), Creatinine \< 1.5 x ULN, Serum Na, K+, Mg2+, Phosphate and Ca2+ \> or = to Lower Limit of Normal (LLN);
• An interval of at least 2 weeks between prior surgical resection (1 week for biopsy) and initiation of study regimen;
• An interval of at least 12 weeks from completion of standard, daily XRT, unless one of the following occurs: a) new area of enhancement on MRI imaging that is outside the XRT field; b) biopsy proven recurrent tumor; c) radiographic evidence of progressive tumor on 2 consecutive scans at least 4 weeks apart;
• An interval of at least 4 weeks from prior chemotherapy (except nitrosoureas which require 6 weeks) unless there is unequivocal evidence of tumor progression and the patient has recovered from all anticipated toxicities from prior therapy;
• An interval of a least 14 days from exposure to investigational agents, unless there is unequivocal evidence of tumor progression and the patients has recovered from all anticipated toxicities from prior therapy;
• Signed written informed consent including HIPAA according to institutional guidelines. A signed informed consent must be obtained prior to any study specific procedures;
• If sexually active, patients will take contraceptive measures for the duration of the treatments and for 3 months following discontinuation of dasatinib and TMZ;
• Women of childbearing potential must have a negative serum or urine pregnancy test (sensitivity \< or = to 25IU HCG/L) within 72 hours prior to the start of study drug administration.

You may not qualify if:

• Prior dasatinib. Imatinib mesylate in the prior three months;
• Grade 3 or greater toxicity related to prior TMZ therapy;
• Prior progression on protracted daily TMZ;
• Pregnancy or breast feeding;
• History of significant concurrent illness;
• More than 3 prior episodes of progressive disease;
• Significant cardiac disease including any of the following:
• congestive heart failure \> class II NYHA;
• unstable angina (anginal symptoms at rest);
• new onset angina (began within the last 3 months);
• myocardial infarction within the past 6 months;
• any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
• uncontrolled congestive heart failure; diagnosed congenital long QT syndrome; prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec);
• Excessive risk of bleeding as defined by stroke within the prior 6 months, history of CNS or intraocular bleed, or septic endocarditis;
• Female patients who are pregnant or breastfeeding, or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to administration of study regimen). Sexually active women of childbearing potential (WOCBP) must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy;

Sponsors & Collaborators

• Annick Desjardins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• Duke University Medical Center Clinical Trials
• The Preston Robert Tisch Brain Tumor Center at Duke

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Astrocytoma; Oligodendroglioma; Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Annick Desjardins, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assist Professor of Medicine-Neurology

Study Record Dates

• First Submitted: May 4, 2008
• First Posted: August 14, 2008
• Study Start: June 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2012
• Last Updated: November 21, 2012

Record last verified: 2012-11

Locations

US (1)