Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
|Eligible Ages||18 Years and Over|
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 =< institutional upper limit of normal - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal; if above the institutional upper limit of normal but =< 3 times institutional upper limit of normal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient - Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal - Activated partial thromboplastin time (APTT)/partial thromboplastin time (PTT) =< 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 (except lymphopenia) 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 AZD1775 (adavosertib) are ineligible; the AZD1775 (adavosertib) 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 AZD1775 (adavosertib) - Patients may not be on drugs known to be moderate or potent inhibitors/inducers of 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 because AZD1775 (adavosertib) has potential for teratogenic or abortifacients effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD1775 (adavosertib), breastfeeding should be discontinued if the mother is treated with AZD1775 (adavosertib) - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD1775 (adavosertib); in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|National Cancer Institute (NCI)|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Eudocia Q Lee|
|Principal Investigator Affiliation||National Cancer Institute (NCI)|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Overall Status||Active, not recruiting|
The disease, disorder, syndrome, illness, or injury that is being studied.
|Glioblastoma, Recurrent Glioblastoma|
- I. To determine the maximum tolerated doses (MTD) of AZD1775 (adavosertib) in combination with the current standard of care (radiotherapy/temozolomide for concomitant therapy and temozolomide for adjuvant therapy) for treating patients with newly diagnosed glioblastoma.
- II. To define the MTD of AZD1775 (adavosertib) in combination with 6 weeks of daily (Monday-Friday [M-F]) radiotherapy (RT) and concomitant temozolomide (TMZ) administered at 75 mg/m^2/day in patients with newly diagnosed glioblastoma.
- III. To define the MTD of AZD1775 (adavosertib) in combination with adjuvant TMZ administered at 150 mg/m^2/day-200 mg/m^2/day for 5 days every 28 days in patients with glioblastoma after concurrent RT/TMZ.
- I. To characterize the safety profile of AZD1775 (adavosertib) in combination with RT and concomitant TMZ (Arm 1) and AZD1775 (adavosertib) with adjuvant TMZ (Arm 2) in patients with newly diagnosed glioblastoma.
- II. To assess the pharmacokinetic (PK) profile of AZD1775 (adavosertib) in combination with upfront radiation/TMZ and adjuvant TMZ in patients with newly diagnosed glioblastoma.
- I. To determine the intratumoral concentration of AZD1775 (adavosertib) achieved in patients treated with the putative MTD.
- II. To characterize the time course of AZD1775 (adavosertib) in extracellular fluid within brain tumors following a single oral dose of drug by microdialysis.
- III. To characterize the pharmacodynamic effects of AZD1775 on tumor through immunohistochemistry (IHC) analysis of pRb (S807/811), proliferation (e.g. Ki-67), pCDC2, Wee1, and apoptosis (e.g. cleaved caspase 3) on resected tumors exposed to drug.
- IV. To characterize MGMT methylation and P53 pathway status, also P-gp and wee1 expression levels in patients with newly diagnosed glioblastoma treated with standard therapy in combination with AZD1775 (adavosertib).
- V. To explore and analyze adaptive resistance mechanisms to AZD1775 using proteogenomics, and connect this data to spatially resolved drug distribution through targeted, imaging-based quantification of drug efficacy and tumor response.
Experimental: Arm I (adavosertib, temozolomide, radiation)
INITIATION CYCLE: Patients receive adavosertib PO on days 1, 3, and 5 or 1-5 weekly and temozolomide PO QD for 6 weeks. Patients also undergo concurrent radiation therapy 5 days per week for 6 weeks. MAINTENANCE CYCLES: Beginning in week 10, patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Experimental: Arm II (adavosertib, temozolomide)
Patients receive adavosertib PO QD on days 1, 3, and 5 or 1-5 weekly, and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Drug: - Adavosertib
Radiation: - Radiation Therapy
Undergo radiation therapy
Drug: - Temozolomide
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Henry Ford Hospital
Detroit, Michigan, 48202
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232