Hydroxychloroquine, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
|ClinicalTrials.gov Identifier: NCT00486603|
Recruitment Status : Unknown
Verified May 2012 by Sidney Kimmel Comprehensive Cancer Center.
Recruitment status was: Active, not recruiting
First Posted : June 14, 2007
Last Update Posted : May 2, 2012
RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving hydroxychloroquine together with temozolomide and radiation therapy may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with radiation therapy and temozolomide and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors||Drug: hydroxychloroquine Drug: temozolomide Genetic: mutation analysis Genetic: polymerase chain reaction Other: immunologic technique Other: laboratory biomarker analysis Other: pharmacological study Procedure: adjuvant therapy Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy||Phase 1 Phase 2|
- Determine the maximum tolerated dose of hydroxychloroquine when administered in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma multiforme. (Phase I)
- Assess the toxicity of this regimen in these patients. (Phase I)
- Determine the overall survival of patients treated with this regimen. (Phase II)
- Assess the frequency of toxicity of this regimen in these patients. (Phase II)
- Evaluate the pharmacokinetics and pharmacodynamics of this regimen in these patients.
- Correlate the average change in autophagic vesicles from baseline with genotype, toxicity, and clinical outcomes.
- Correlate the presence of TP53 and PTEN genes and BECN1 with toxicity and clinical outcomes.
OUTLINE: This is a multicenter, open-label, phase I, dose-escalation study of hydroxychloroquine followed by a phase II study.
- Initiation therapy: Patients receive oral temozolomide daily for 6 weeks and undergo conformal or intensity-modulated radiotherapy 5 days a week for 6 weeks. Patients also receive oral hydroxychloroquine daily for 10 weeks beginning concurrently with temozolomide and radiotherapy.
Cohorts of 3-6 patients receive escalating doses of hydroxychloroquine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Maintenance therapy: Beginning 28 days after completion of radiotherapy, patients receive oral temozolomide on days 1-5 and oral hydroxychloroquine on days 1-28. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive hydroxychloroquine alone as above in the absence of disease progression or unacceptable toxicity.
- Phase II:
- Initiation therapy: Patients receive hydroxychloroquine at the MTD determined in phase I, temozolomide, and radiotherapy as in phase I.
- Maintenance therapy: Patients receive hydroxychloroquine at the MTD determined in phase I and temozolomide as in phase I.
Patients undergo blood and tissue sample collection periodically for pharmacological and correlative studies. Samples are analyzed for the mutational status of TP53 and PTEN genes and copy number of BECN1 via PCR; changes in autophagy protein LC3 via gel electrophoresis; and differences in the formation of LC3-II via immunoblotting.
After completion of study treatment, patients are followed every 2 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||94 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Hydroxychloroquine in Conjunction With Radiation Therapy and Concurrent and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme|
|Study Start Date :||October 2007|
|Estimated Primary Completion Date :||January 2013|
- Maximum tolerated dose of hydroxychloroquine (Phase I) [ Time Frame: continous ]
- Safety [ Time Frame: continous ]
- Overall survival [ Time Frame: continous ]
- Death [ Time Frame: continous ]
- Toxicity and tolerability (Phase I) [ Time Frame: continous ]
- Frequency of toxicity (Phase II) [ Time Frame: continous ]
- Pharmacokinetics and pharmacodynamics of hydroxychloroquine [ Time Frame: continous ]
- Correlation of the presence of TP53 and PTEN genes and BECN1 with toxicity and clinical outcomes [ Time Frame: continous ]
- Correlation of the average change in autophagic vesicles from baseline with genotype, toxicity, and clinical outcomes [ Time Frame: continous ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00486603
|United States, Alabama|
|UAB Comprehensive Cancer Center|
|Birmingham, Alabama, United States, 35294|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida|
|Tampa, Florida, United States, 33612-9497|
|United States, Georgia|
|Winship Cancer Institute of Emory University|
|Atlanta, Georgia, United States, 30322|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Michigan|
|Josephine Ford Cancer Center at Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|United States, Ohio|
|Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|Study Chair:||Myrna Rosenfeld, MD, PhD||Abramson Cancer Center of the University of Pennsylvania|