Dexanabinol in Patients With Brain Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of California, San Diego
Sponsor:
Collaborator:
e-Therapeutics PLC
Information provided by (Responsible Party):
Santosh Kesari, M.D., Ph.D., University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01654497
First received: July 16, 2012
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

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).

Condition Intervention Phase
Brain Cancer
Drug: Dexanabinol
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Sequential Cohort, Open-Label, Dose-escalation Study of the Safety and CNS Pharmacokinetics of Dexanabinol in Patients With Brain Cancer

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Rate of dose limiting toxicities and the maximum tolerated dose (MTD) of weekly dexanabinol [ Time Frame: first 28 days of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Treatment-emergent adverse events [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
    description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness

  • Objective response rate and best overall response rate over time as assessed by the RANO criteria [ Time Frame: approximately 6 months to 1 year ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: June 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexanabinol Drug: Dexanabinol

Dexanabinol: intravenous infusion over 3 hours, weekly (i.e., Day 1, 8, 15 and 22 of a 28-day cycle)

Four dosing cohorts are initially 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


Detailed Description:

Protection from apoptosis is a key survival factor for cancer cells. Dexanabinol is under investigation as a novel anti-cancer therapy based on its tumoricidal activity observed in vitro and in vivo, presumably due to inhibitory activity against NFĸB, TNFα, COX-2 and additional putative targets suck as HAT, FAT and cyclin dependent kinases. Targeted induction of apoptosis in cancer cells versus normal cells provides an attractive strategy for the treatment of brain cancer, a pernicious disease with debilitating neurological side effects and poor prognoses. A single intravenous dosing of dexanabinol has demonstrated safety in humans. Therefore, we are conducting a phase I dose escalation study to examine the safety of multiple dosing of dexanabinol and drug penetration into the brain, and to determine a suitable dose for moving into a phase II trial for efficacy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01654497

Contacts
Contact: Angel Nguyen 858-822-0201 anguyen85@ucsd.edu
Contact: Joanne Brechlin 858-822-5352 Jbrechlin@ucsd.edu

Locations
United States, California
Moores UCSD Cancer Center Recruiting
La Jolla, California, United States, 92093-0698
Principal Investigator: Santosh Kesari, MD, Ph.D.         
Sponsors and Collaborators
Santosh Kesari, M.D., Ph.D.
e-Therapeutics PLC
Investigators
Principal Investigator: Santosh Kesari, MD, PhD University of California Medical Center
  More Information

No publications provided

Responsible Party: Santosh Kesari, M.D., Ph.D., Associate Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01654497     History of Changes
Other Study ID Numbers: 111827
Study First Received: July 16, 2012
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
Brain
Glioma
glioblastoma
metastases
cancer
ETS2101
leptomeningeal
astrocytoma
oligodendroglioma
meningioma

Additional relevant MeSH terms:
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dronabinol
HU 211
Hallucinogens
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Arrhythmia Agents
Cardiovascular Agents
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on September 22, 2014