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Dasatinib Plus Radiation Therapy/Temozolomide in Newly-Diagnosed Glioblastoma | Clinical Trials | Clareo Health

TERMINATEDPHASE1

Dasatinib Plus Radiation Therapy/Temozolomide in Newly-Diagnosed Glioblastoma

Phase I/II Trial of Dasatinib (Sprycel) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma

NCT00895960•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

Phase I: Primary Objectives: -To define the maximum tolerated dose (MTD) of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ) administered at 75 mg/m\^2/day in patients with newly-diagnosed glioblastoma (GBM). Secondary Objectives: * To characterize the safety profile of dasatinib (Sprycel) in combination with radiotherapy (RT) and concomitant TMZ in patients with newly-diagnosed GBM. * To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant TMZ in patients with glioblastoma after RT. STUDY DID NOT PROGRESS TO PHASE II PORTION. Phase II: Primary Objectives: -To determine the effectiveness of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ) administered at 75 mg/m\^2/day followed by adjuvant temozolomide with concurrent dasatinib in patients with newly-diagnosed glioblastoma (GBM) as measured by overall survival. Secondary Objectives: * To determine the efficacy of this treatment as measured by radiographic response (RR), progression-free survival (PFS) and time to progression (TTP). * To characterize the safety profile of dasatinib (Sprycel) in combination with RT and concomitant TMZ in patients with newly-diagnosed GBM. * To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant TMZ in patients with GBM after RT. Exploratory Objectives: -To correlate tumor genotype, tumor expression of dasatinib target proteins (e.g. Src, EphA2, c-kit and PDGFR), and PTEN levels with response to therapy with dasatinib and temozolomide.

Detailed Description

PHASE I The Study Drugs: Dasatinib is designed to change the function of certain genes. By changing the function of these genes, it may prevent cancer from growing and spreading. It is also designed to block or lower the activity of one or more tumor-causing proteins responsible for the uncontrolled growth of tumor cells, which may result in shrinking or stopping tumor growth. Temozolomide is designed to kill cancer cells by damaging DNA (the genetic material of cells). The damaged DNA may cause tumor cell death. Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a dose level of dasatinib based on when you joined this study. Up to 2 dose levels of dasatinib will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of dasatinib given in combination with temozolomide is found. All the groups will take the same dose level of temozolomide for the entire study. The amount of study drugs you receive may change if you experience side effects. If at any time you experience any intolerable side effects, tell the study doctor right away. Study Drug Administration: During Radiation: As a part of standard of care, you will receive radiation therapy Monday-Friday for a total of 30 radiation treatments (about 6 weeks). Every day while you are receiving radiation, you will take the temozolomide by mouth once a day for up to a maximum of 7 weeks. You should swallow temozolomide whole, one right after the other, without chewing them. If you vomit while taking temozolomide, you cannot take more capsules before the next scheduled dose. They should be taken on an empty stomach (at least 1 hour before and 2 hours after eating) with 1 cup (about 8 oz.) of water. Every day while you are receiving radiation, you will take dasatinib by mouth 1 time a day for up to a maximum of 7 weeks. You should take dasatinib without food (1 hour before or 2 hours after eating), with at least 1 cup (8 oz.) of water. After Radiation: After the radiation therapy ends, every day, you will continually take dasatinib by mouth 1 time a day. You will not take temozolomide for about 4 weeks after the radiation therapy ends. After 4 weeks, you will begin taking temozolomide 1 time a day, by mouth, on Days 1-5 of each 28 day study cycle. Study Visits: Four (4) weeks after the end of radiation, then every 4 weeks after that, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your vital signs. * You will have a neurological exam. * You will have a performance status evaluation. * You will be asked about any drugs you may be taking and if you have experienced any side effects. * Blood (about 1 teaspoon) will be drawn to check your blood's ability to clot normally. Every week for the first 6 weeks, then every 4 weeks after that, you will be asked if you have experienced any side effects. If you are taking an anti-seizure drug, every 2 weeks for the first 6 weeks and then every 4 weeks after that, blood (about 1 teaspoon) will be drawn to check the levels of anti-seizure drug in your blood. At Week 6, then before each cycle after radiation for the first 6 cycles, you will have an ECG. Every week for the first 6 weeks, then on Days 1 and 22 of every cycle after radiation, blood (about 3 teaspoons) will be collected for routine tests. Four (4) weeks after the end of radiation, then every 8 weeks after that, you will have an MRI scan to check the status of the disease. Length of Study: You may continue taking temozolomide for up to 12 cycles. You may continue taking dasatinib for as long as you are benefitting. You will be taken off study early if the disease gets worse or you experience intolerable side effects. End-of-Study Visit: After you go off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed: * Your complete medical history will be recorded. * You will have a physical exam. * You will have a performance status evaluation. * You will be asked about any drugs you may be taking and if you have experienced any side effects. * You will have a neurological exam. * Blood (about 3 1/2 teaspoons) will be collected for routine tests and to check your blood's ability to clot normally. * If you are taking an anti-seizure drug, blood (about 1 teaspoon) will be drawn to check the level of anti-seizure drug in your blood. Long-Term Follow-up visit: After the end-of-study visit, the study team/staff will contact you by telephone every 3 months to check how you are doing. Each phone call will take about 5 minutes. This is an investigational study. Temozolomide is FDA approved and commercially available for the treatment of brain tumors. Dasatinib is FDA approved and commercially available for the treatment of some types of leukemia, but it is experimental for use in brain tumors. In addition, the combination of temozolomide and dasatinib is experimental for use in brain tumors. At this time, the combination is only being used in research. Up to 72 participants will take part in this study. Up to 72 will be enrolled at M. D. Anderson.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•2. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
•3. Diagnosis will have been established by biopsy or resection 14-28 days prior to registration. In order to permit healing, patients should not receive Day 1 of treatment until at least 14 days after surgery.
•4. Patients must not have had prior cranial RT
•5. Patients must have a plan to begin partial brain RT on the same day as the first dasatinib dose and the first dose of TMZ. Radiotherapy can be performed at either MD Anderson or outside facilities. Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180 to 200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. Stereotactic radiosurgery and brachytherapy will not be allowed.
•6. Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
•7. Patients must be \>/= 18 years old.
•8. A contrast enhanced brain scan should be performed within 14 days prior to registration and on a corticosteroid dose that has been stable or decreasing for at least 5 days. If the corticosteroid dose is increased between the date of imaging and registration, then a new baseline MRI/CT is required. The same type of scan, i.e., MRI or CT, must be used throughout the period of protocol treatment for tumor measurement. The use of MRI rather than CT is preferred.
•9. Patients must have a Karnofsky performance status of \>/= 60.
•10. Patients must have adequate bone marrow function (WBC \>/= 3,000/µl, ANC \>/= 1,500/mm\^3, platelet count of \>/= 100,000/mm\^3, and hemoglobin \>/= 10 gm/dl), adequate liver function (SGOT, SPGT and bilirubin \</= 2 times ULN), serum Na, K+, Mg\^2+, phosphate and Ca\^2+ \>/= Lower Limit of Normal (LLN) and adequate renal function (creatinine \</= 1.5 mg/dL or creatinine clearance \>/= 60 cc/min/1.73 m\^2) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
•11. Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while enrolled in the study.
+1 more criteria

Exclusion Criteria

•1. Patients must not have received prior Gliadel wafers.
•2. Patients must not have received any investigational agents within 30 days prior to commencing study treatment.
•3. Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
•4. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
•5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
•6. Patients with the following invasive procedures: a) Major surgical procedure, open biopsy or significant traumatic injury \< 14 days prior to Day 1 therapy b) Anticipation of need for major surgical procedures during the course of the study c) Core biopsy within 7 days prior to Day 1 therapy.
•7. Patients must not be pregnant/breastfeeding and must agree to practice adequate contraception. Breastfeeding should be discontinued if the mother is treated with dasatinib.
•8. Patients with clinically significant cardiovascular disease: a) History of ischemic or hemorrhagic stroke within past 6 months b) Uncontrolled hypertension, defined as blood pressure \>140/90 mm Hg or systolic BP \>180 mm Hg if diastolic blood pressure \<90 mm Hg, on at least 2 repeated determinations on separate days within past 3 months c) Myocardial infarction, CABG or unstable angina within past 6 months d) New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months
•9. ( 8. continued) e) Clinically significant peripheral vascular disease within past 6 months f) Pulmonary embolism, DVT, or other thromboembolic event within past 6 months. g) Diagnosed congenital long QT syndrome h) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) i) Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec) j) Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
•10. Evidence of bleeding diathesis or coagulopathy or INR \>1.5. History of significant bleeding disorder unrelated to cancer, including: a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) c) Ongoing or recent (\</= 3 months) significant gastrointestinal bleeding
+9 more criteria

Locations (1)

UT MD Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

May 7, 2009

Primary Completion Date

August 1, 2013

Completion Date

August 1, 2013

Last Updated

November 8, 2018

Enrollment

ACTUAL participants

Conditions

GlioblastomaCNS DiseaseBrain Diseases

Interventions

Dasatinib

DRUG

RT (Radiotherapy)

RADIATION

TMZ (Temozolomide)

DRUG

Targeted Pediatric High-Grade Glioma Therapy

NCT05839379

High Grade GliomaDiffuse Intrinsic Pontine Glioma+7 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: November 8, 2018Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Dasatinib Plus Radiation Therapy/Temozolomide in Newly-Diagnosed Glioblastoma

Inclusion Criteria

Exclusion Criteria

Targeted Pediatric High-Grade Glioma Therapy

Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma

Collection of Blood and Urine Samples in Patients Receiving Radiation Therapy for Glioblastoma Multiforme

Hypofractionation Trial of Re-irradiation in Good Prognosis Recurrent Glioblastoma

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Study of TLX101-Tx Plus Standard of Care (SoC) Versus SoC Alone for the Treatment of Patients With Recurrent Glioblastoma