- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01654497
Dexanabinol in Patients With Brain Cancer
A Phase I, Sequential Cohort, Open-Label, Dose-escalation Study of the Safety and CNS Pharmacokinetics of Dexanabinol in Patients With Brain Cancer
The purpose of this study is to try to determine the maximum safe dose of dexanabinol that can be administered to people with brain cancer. Other purposes of this study are to:
- find out what effects (good and bad) dexanabinol has;
- see how much drug gets into the body by collecting blood and cerebrospinal fluid for use in pharmacokinetic (PK) studies;
- learn more about how dexanabinol might affect the growth of cancer cells;
- look at biomarkers (biochemical features that can be used to measure the progress of disease or the effects of a drug).
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
La Jolla, California, United States, 92093-0698
- Moores UCSD Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically or radiologically confirmed diagnosis of brain cancer:
- glioblastoma (GBM),
- anaplastic astrocytoma (AA),
- anaplastic oligodendroglioma (AO),
- anaplastic mixed oligoastrocytoma (AMO),
- low grade gliomas,
- brain metastases,
- meningiomas, or
- leptomeningeal metastases
- Has failed prior standard therapy including maximal safe surgical resection, radiation therapy (when appropriate for the specific cancer type), and systemic therapy.
- For diagnosis of GBM: has undergone at least one prior surgical gross-total or subtotal tumor resection, a course of postoperative radiation therapy with concurrent temozolomide, and at least 2 cycles of maintenance temozolomide.
- For diagnosis of meningioma: has no other option of standard therapy such as surgical resection (partial or total resection) or radiation.
- Has progression of brain cancer and measurable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
- Age ≥ 18 years.
- Karnofsky Performance Status ≥ 60%. (Appendix A). Subjects must have a life expectancy of equal to or greater than 8 weeks.
- Organ and Marrow Function Requirements
Hematology:
- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9.0 g/dL
- White blood cell (WBC) count ≥ 3.0 x 109/L
Biochemistry:
- AST/SGOT and ALT/SGPT ≤ 2.5 x institution's ULN
- Total bilirubin ≤ 1.5 x institution's ULN
- Serum creatinine ≤ 1.5 x institution's ULN or 24-hour creatinine clearance ≥ 50 ml/min
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related
- Estimated GFR > 50 ml/min (based on Wright formula)
Coagulation:
- INR < 1.5 x institution's ULN
PT/aPTT within institution's normal range, unless receiving therapeutic low molecular weight heparin
- Contraception Woman of child-bearing potential and man with partners of child-bearing potential agrees to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days following completion of therapy.
- Woman of child-bearing potential has negative pregnancy test before the initiation of study drug dosing.
Exclusion Criteria:
- Current or anticipated use of other investigational agents.
- Current or anticipated use of enzyme-inducing anti-epileptic drugs (EIAED).
Insufficient time for recovery from prior therapy:
- less than 28 days from any investigational agent,
- less than 28 days from prior cytotoxic therapy (except 23 days from prior temozolomide, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration), and
- less than 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count).
- Less than 4 weeks from surgery or insufficient recovery from surgical-related trauma or wound healing.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to dexanabinol.
- History of allergic reactions to medicines containing polyoxyethylated castor oil that are not controlled with premedications.
- Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection).
- Electrolyte abnormality that cannot be corrected to normal levels prior to initiating study drug.
- Known diagnosis of human immunodeficiency virus (HIV) infection.
Impaired cardiac function including any of the following:
- Congenital long QT syndrome or a known family history of long QT syndrome;
- History or presence of clinically significant ventricular or atrial tachyarrhythmias
- Clinically significant resting bradycardia (< 50 beats per minute)
- Inability to monitor the QT interval by ECG
- QTc > 450 msec on baseline ECG. If QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- Myocardial infarction within 1 year of starting study drug
- Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
- Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dexanabinol
|
Dexanabinol: intravenous infusion over 3 hours, weekly (i.e., Day 1, 8, 15 and 22 of a 28-day cycle) Nine dosing cohorts are planned, with the option to enroll additional cohorts based on safety and PK data. Dose Level 1: 2 mg/kg Dose Level 2: 4 mg/kg Dose Level 3: 8 mg/kg Dose Level 4: 16 mg/kg Dose Level 5: 24 mg/kg Dose Level 6: 28 mg/kg Dose Level 7: 36 mg/kg Dose Level 8: 40 mg/kg Dose Level 9: 44 mg/kg |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Rate of dose limiting toxicities and the maximum tolerated dose (MTD) of weekly dexanabinol
Time Frame: first 28 days of treatment
|
first 28 days of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: up to 5 years
|
up to 5 years
|
|
Treatment-emergent adverse events
Time Frame: 7 months
|
description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness
|
7 months
|
Objective response rate and best overall response rate over time as assessed by the RANO criteria
Time Frame: approximately 6 months to 1 year
|
approximately 6 months to 1 year
|
|
Overall Survival
Time Frame: up to 5 years
|
up to 5 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Santosh Kesari, MD, PhD, University of California Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Brain Neoplasms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Antiemetics
- Gastrointestinal Agents
- Neuroprotective Agents
- Protective Agents
- HU 211
Other Study ID Numbers
- 111827
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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