Brain CancerPhase 1NCT01654497
Dexanabinol in Patients With Brain Cancer
A Phase 1 study testing Dexanabinol in people with Brain Cancer, run by Santosh Kesari, M.D., Ph.D. at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Cancer
- What is being tested?
- Dexanabinol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or radiologically confirmed diagnosis of brain cancer:
- glioblastoma (GBM),
- anaplastic astrocytoma (AA),
- anaplastic oligodendroglioma (AO),
- anaplastic mixed oligoastrocytoma (AMO),
- low grade gliomas,
Show all 32Show fewer
- 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.
Who cannot join
- 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).
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Moores UCSD Cancer Center
La Jolla, California, 92093-0698
About this study
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
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).
Read the 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.
- Conditions
- Brain Cancer
- Being tested
- Dexanabinol
- Keywords
- Brain, Glioma, glioblastoma, metastases, cancer, ETS2101, leptomeningeal, astrocytoma, oligodendroglioma, meningioma
- Medical subject headings
- Brain Neoplasms, Glioma, Glioblastoma, Neoplasm Metastasis, Neoplasms, Astrocytoma, Oligodendroglioma, Meningioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexanabinolDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Dexanabinol | Experimental | Not described Receives: Drug: Dexanabinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities and the maximum tolerated dose (MTD) of weekly dexanabinol
Measured: first 28 days of treatment
Secondary outcomes (4)
Treatment-emergent adverse events
description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness
Measured: 7 months
Objective response rate and best overall response rate over time as assessed by the RANO criteria
Measured: approximately 6 months to 1 year
Progression free survival
Measured: up to 5 years
Overall Survival
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2012 (estimated)
- Study startJun 2012
- Primary completionSep 2015
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Santosh Kesari, M.D., Ph.D.
- Sponsor type
- University, hospital or other
- Collaborators
- e-Therapeutics PLC
- Responsible party
- Sponsor-investigator, Santosh Kesari, M.D., Ph.D., University of California, San Diego
- Investigators
- Santosh Kesari, MD, PhD, Principal investigator, University of California Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01654497
- Sponsor's protocol ID
- 111827
- Status last verified
- Nov 2019
- First submitted
- 16 Jul 2012
- Last updated
- 14 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01654497
- Acronym / sponsor ID
- 111827
- Conditions
- Brain Cancer
- Keywords
- Brain, Glioma, glioblastoma, metastases, cancer, ETS2101, leptomeningeal, astrocytoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Santosh Kesari, M.D., Ph.D.University, hospital or other
- Collaborators
- e-Therapeutics PLC
- Study start
- Jun 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 31 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dexanabinol | Experimental | Drug: Dexanabinol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Histologically or radiologically confirmed diagnosis of brain cancer:
- 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.
Key exclusion criteria (21 listed)
- 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 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexanabinolDexanabinol: 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 | Drug | Dexanabinol |
Primary outcome
Rate of dose limiting toxicities and the maximum tolerated dose (MTD) of weekly dexanabinol
Time frame: first 28 days of treatment
4 secondary outcomes
Treatment-emergent adverse events
Time frame: 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
Progression free survival
Time frame: up to 5 years
Overall Survival
Time frame: up to 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
Related trials for Brain Cancer
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Santosh Kesari, MD, PhD principal investigator
University of California Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dexanabinol in people with Brain Cancer, run by Santosh Kesari, M.D., Ph.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of dose limiting toxicities and the maximum tolerated dose (MTD) of weekly dexanabinol (time frame: first 28 days of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2019.