WEE1 Inhibitor MK-1775, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed or Recurrent Glioblastoma Multiforme

Status: Recruiting
Phase: Phase 1
Diagnosis: Brain/Neuro Cancer: Newly Diagnosed, Brain/Neuro Cancer: Recurrent Glioblastoma
NCT ID: NCT01849146 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-311

 

This phase I trial studies the side effects and best dose of WEE1 inhibitor MK-1775 when given together with radiation therapy and temozolomide in treating patients with newly diagnosed or recurrent glioblastoma multiforme. WEE1 inhibitor MK-1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving WEE1 inhibitor MK-1775 together with radiation therapy and temozolomide may be an effective treatment for glioblastoma multiforme.

 

Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Jorg Dietrich, M.D., Massachusetts General Hospital

Site-responsible Investigators:
Brian Alexander, MD, MPH, Brigham and Women's Hospital

Contacts:
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100
Dana-Farber Cancer Institute: Lisa Doherty, ldoherty1@partners.org

Eligibility Criteria

Inclusion Criteria: - Patients must have a tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of glioblastoma completed and signed by a pathologist - Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others) - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Hemoglobin >= 9 g/dL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 × institutional upper limit of normal - Creatinine within normal institutional limits OR creatinine clearance >= 60 ml/min/1.73m^2 for patients with creatinine levels above institutional normal - Activated partial thromboplastin time (APTT) =< 1.5 x institutional upper limit of normal - Patients must be able to provide written informed consent - Patients must have magnetic resonance imaging (MRI) within 21 days of starting treatment - Women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to use two birth control methods (either two barrier methods or a barrier method plus a hormonal method) or abstinence prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years - Patients must be maintained on a stable corticosteroid regimen (no increase for 5 days) prior to the start of treatment - Patients must be able to swallow whole capsules - PHASE I PATIENTS: - Must have histologically proven glioblastoma - Must have recovered from the immediate post-operative period - Patients going on Arm 1 or combination dose cohort must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes [TIL], lymphokine-activated killer [LAK] or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed - Patients going on Arm 2 must have received planned treatment with radiation therapy and concomitant temozolomide at least 28 days but no more than 49 days prior to starting treatment on this study; patients must have received at least 80% of planned temozolomide and radiation therapy with no grade 3 or grade 4 toxicity attributed to the temozolomide; Arm 2 patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; prior Gliadel Wafers are allowed; glucocorticoid therapy is allowed - INTRATUMORAL DRUG DISTRIBUTION STUDY PATIENTS: - Patients must have prior histologically proven glioblastoma that is progressive or recurrent following radiation therapy +/- chemotherapy - Patients must be undergoing repeat surgery that is clinically indicated as determined by their care providers - Patients must have measurable contrast-enhancing progressive or recurrent glioblastoma by MRI within 21 days of starting treatment; patient must be able to tolerate MRIs - Patients may have an unlimited number of prior therapy regimens - Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible: - 12 weeks from the completion of radiation - 6 weeks from a nitrosourea chemotherapy - 3 weeks from a non-nitrosourea chemotherapy - 4 weeks from any investigational (not Food and Drug Administration [FDA]-approved) agents - 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., Tarceva, hydroxychloroquine, bevacizumab, etc.) Exclusion Criteria: - Patients receiving any other investigational agents are ineligible - Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or MK-1775 are ineligible; the MK-1775 Investigator Brochure and the temozolomide package insert can be referenced for more information - Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol; patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of MK-1775 - Patients may not be on drugs known to be moderate or potent inhibitors/inducers of cytochrome P450 3A4 (CYP3A4), sensitive substrates of CYP3A4, or substrates of CYP3A4 with narrow therapeutic windows - Patients may not be on anti-coagulants (warfarin, etc.) other than low-molecular weight heparin (LMWH) - Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible - Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-1775 - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
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