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
Verified date | June 2019 |
Source | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 92 |
Est. completion date | January 2014 |
Est. primary completion date | June 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 120 Years |
Eligibility |
DISEASE CHARACTERISTICS: - Histologically confirmed grade IV supratentorial astrocytoma (glioblastoma multiforme) - Newly diagnosed disease - Diagnosis must have been made by biopsy or resection = 3 months prior to study entry INCLUSION CRITERIA: - Patients must be at least 18 years of age. - Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme), established by biopsy or resection not more than 3 months prior to registration. - Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor. Glucocorticoid therapy is allowed. - 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). - Patients must have the following hematologic, renal and liver function (i.e. absolute neutrophil count > 1500/mm3, platelets > 100,000/mm3, creatinine = 2 times the upper limits of normal (ULN) total bilirubin = 1.5 mg/dl, ALT and AST = 4 times above the upper limits of the institutional norm. - Patients must be able to provide written informed consent. - Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant. - Patients must have a Mini Mental State Exam (MMSE) score of > 15. - Patients must have tumor tissue form completed and signed by a pathologist. See section 9.5.2 for details. - Prior concurrent therapy: - No prior radiotherapy, chemotherapy, immunotherapy, biologic agents (e.g., immunotoxins, immunoconjugates, antisense agents, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cell therapy, or gene therapy), or hormonal therapy for brain tumor - No prior polifeprosan 20 with carmustine implant (Gliadel wafer) or GliaSite® brachytherapy - No concurrent cytochrome P450 enzyme-inducing anticonvulsant drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine) - No other concurrent chemotherapeutic or investigational agents for this cancer - Concurrent glucocorticoids allowed EXCLUSION CRITERIA: - Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety. - Patients who are pregnant or breast-feeding. - Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or investigational agents). - Patients with a concurrent or prior malignancy, unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for five years are eligible for this study. - Patients who have received Gliadel wafers or GliaSite brachytherapy are not eligible. - Due to risk of disease exacerbation patients with porphyria are not eligible. - Due to risk of disease exacerbation patients with psoriasis are ineligible unless the disease is well controlled and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations. - Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e. phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine). - Patients with previously documented macular degeneration or diabetic retinopathy. |
Country | Name | City | State |
---|---|---|---|
United States | Winship Cancer Institute of Emory University | Atlanta | Georgia |
United States | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland |
United States | University of Alabama at Birmingham Comprehensive Cancer Center | Birmingham | Alabama |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | Case Comprehensive Cancer Center | Cleveland | Ohio |
United States | Josephine Ford Cancer Center at Henry Ford Hospital | Detroit | Michigan |
United States | Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania |
United States | H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | Tampa | Florida |
United States | Wake Forest University Comprehensive Cancer Center | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | National Cancer Institute (NCI) |
United States,
Rosenfeld MR, Ye X, Supko JG, Desideri S, Grossman SA, Brem S, Mikkelson T, Wang D, Chang YC, Hu J, McAfee Q, Fisher J, Troxel AB, Piao S, Heitjan DF, Tan KS, Pontiggia L, O'Dwyer PJ, Davis LE, Amaravadi RK. A phase I/II trial of hydroxychloroquine in con — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | (Phase I) Maximum Tolerated Dose (MTD) of Hydroxychloroquine (HCQ) | Number of participants who tolerated doses of HCQ without dose limiting toxicity. The highest dose at which participants did not experience dose limiting toxicity was determined as the MTD. | 10 weeks | |
Primary | (Phase I) Number of Participants Who Experienced Dose Limiting Toxicity (DLT) | Dose limiting toxicity defined as: Any DLT must be a toxicity considered at least possibly related to HCQ. DLTs will include any possibly, probably, or definitely HCQ-related Grade 3 or 4 toxicity. Known or reasonably suspected TMZ hematological toxicities will not be considered dose limiting unless the treating physician considers the toxicity to be exacerbated by HCQ. Nonhematological toxicities: Any Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis) | 10 weeks | |
Primary | (Phase II) Overall Survival | Number of months alive after end of study participation | 2 years | |
Secondary | (Phase II) Number of Participants With Grade 3 and 4 Toxicity | Number of participants experiencing Grade 3 and 4 toxicity, as defined by CTCAE v3.0, with a possible, probable or definite relationship to HCQ, TMZ or both | up to 2 years | |
Secondary | Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition | Number of participants with at least 2 peripheral blood mononuclear cell (PBMC) samples that were amenable to electronmicroscopy (EM) who showed an increase of autophagic vacuoles in cells. | up to 9 weeks | |
Secondary | Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition in Relation to Maximal Concentration (Cmax) of HCQ | Autophagy inhibition is represented by an increase in autophagic vacuoles (AV) in participants with at least 2 peripheral blood mononuclear cell samples that were amenable to EM. | up to 9 weeks | |
Secondary | Pharmacokinetics (PK) of Hydroxychloroquine as Measured by Lag Time (Tlag) | The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model. | up to 276 days | |
Secondary | PK of Hydroxychloroquine as Measured by Oral Clearance (Liters/Hour) From Central Compartment (CL/F) | The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model. | up to 276 days | |
Secondary | PK of Hydroxychloroquine as Measured by Volume of Distribution of Central Compartment (V/F) | The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model. | up to 276 days | |
Secondary | PK of Hydroxychloroquine as Measured by Distribution Volume of Peripheral Compartment (V2/F) | The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model. | up to 276 days | |
Secondary | PK of Hydroxychloroquine as Measured by First-order Absorption Rate Constant (Ka) | The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model. | up to 276 days |
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