Brain and Central Nervous System Tumors Clinical Trial
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
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.
OBJECTIVES:
Primary
- 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)
Secondary
- 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.
- Phase I:
- 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.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT00788125 -
Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors
|
Phase 1/Phase 2 | |
Completed |
NCT00006080 -
Fenretinide in Treating Patients With Recurrent Malignant Glioma
|
Phase 2 | |
Recruiting |
NCT00887146 -
Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
|
Phase 3 | |
Suspended |
NCT00935090 -
3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer
|
N/A | |
Completed |
NCT00621686 -
Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme
|
Phase 2 | |
Completed |
NCT00112502 -
Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme
|
Phase 2 | |
Terminated |
NCT00227032 -
Erlotinib in Treating Patients With Progressive Glioblastoma Multiforme
|
Phase 1 | |
Terminated |
NCT00243022 -
Dietary, Herbal and Alternative Medicine in Glioblastoma Multiforme
|
Phase 2 | |
Active, not recruiting |
NCT00087815 -
Hyperbaric Oxygen Therapy in Treating Patients With Radiation Necrosis of the Brain
|
N/A | |
Active, not recruiting |
NCT00278278 -
Combination Chemotherapy and Radiation Therapy With or Without Methotrexate in Treating Young Patients With Newly Diagnosed Gliomas
|
Phase 3 | |
Completed |
NCT00416819 -
Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Primary CNS Lymphoma
|
N/A | |
Completed |
NCT00052286 -
Modafinil in Treating Fatigue and Behavioral Change in Patients With Primary Brain Cancer
|
N/A | |
Completed |
NCT00006093 -
EMD 121974 in Treating Patients With Progressive or Recurrent Glioma
|
Phase 1/Phase 2 | |
Recruiting |
NCT00004129 -
Phosphorus 32 in Treating Patients With Glioblastoma Multiforme
|
Phase 1 | |
Completed |
NCT00004212 -
DX-8951f in Treating Children With Advanced Solid Tumors or Lymphomas
|
Phase 1 | |
Completed |
NCT00003417 -
Computer Planned Radiation Therapy Plus Chemotherapy in Treating Patients With Glioblastoma Multiforme
|
Phase 1/Phase 2 | |
Completed |
NCT00003173 -
High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors
|
Phase 2 | |
Completed |
NCT00003020 -
LMB-7 Immunotoxin in Treating Patients With Leptomeningeal Metastases
|
Phase 1 | |
Completed |
NCT00008008 -
Thiotepa Followed by Peripheral Stem Cell or Bone Marrow Transplant in Treating Patients With Malignant Glioma
|
Phase 2 | |
Completed |
NCT00003484 -
Radiolabeled Monoclonal Antibody Therapy After Radiation Therapy in Treating Patients With Primary Brain Tumors
|
Phase 1 |