Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Carcinoma, Hepatocellular

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Sorafenib

HU 211

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Protein Kinase Inhibitors

Enzyme Inhibitors

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

Protective Agents

Patients with selected relapsed or refractory tumour types to receive single agent dexanabinol.

Patients with hepatocellular carcinoma to receive dexanabinol in combination with standard chemotherapy.

Patients with pancreatic cancer to receive dexanabinol in combination with standard chemotherapy

Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period

Dexanabinol

Patients will receive Sorafenib at a dose of 400 mg bid (oral administration)

Patients will receive Nab-paclitaxel at a dose of 125mg/m2 intravenous infusion

Nab-paclitaxel

Patients will receive Gemcitabine at a dose of 1000mg/m2 intravenous infusion

This study is a trial of dexanabinol in patients with advanced tumours. The purposes of the protocol are to study different doses of the study drug to determine the maximum safe dose of the drug given in combination with standard chemotherapies and to further understand the safety of the study drug and to measure any reduction in size of patients' cancer tumour(s).

Dexanabinol is a synthetic cannabinoid which has previously undergone clinical trials for traumatic brain injury (TBI) and in subjects undergoing coronary artery bypass surgery. Currently dexanabinol is under investigation for potential anti-tumour activity in patients with advanced tumours.

A Study of Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours

A Phase 1b Study to Assess the Safety and Anti-tumour Activity of Dexanabinol Monotherapy and Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours

Patients will be sequentially assigned to increasing doses of dexanabinol to establish the MTD (or maximum administered dose (MAD)). 3 patients will be enrolled to a cohort to assess each dose level. Dose escalation to a cohort of 3 new patients will occur when all patients in the previous cohort have completed the first cycle i.e. the first four doses followed by observation through to day 29 and no dose limiting toxicity (DLT) has occurred.

AEs will be graded according to the NCI CTCAE v4.03 for cancer clinical trials.

Tumour response evaluation using RECIST 1.1 (assessment by CT or MRI).

e-Therapeutics PLC

Nervous System Diseases

Symptoms and General Pathology

Glioma

Glioblastoma

Brain Neoplasms

Astrocytoma

Meningioma

Oligodendroglioma

Neoplasm Metastasis

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

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

Santosh Kesari, MD, PhD

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).

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.

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

description, timing, grade \[CTCAE v4.03\], severity, seriousness, and relatedness

Santosh Kesari, M.D., Ph.D.

Associate Professor

Analgesics

Psychotropic Drugs

Dronabinol

Hallucinogens

Analgesics, Non-Narcotic

Hormones

Hormone Antagonists

Dexanabinol Dose Level 1

Dexanabinol Dose Level 2

Dexanabinol Dose Level 3

Dexanabinol Dose Level 4

Dexanabinol Dose Level 5

Placebo

Philip Evans, MD

The purpose of this study is to test the safety and observe the pharmacokinetics (distribution and elimination of the drug) of the compound dexanabinol (ETS2101) in healthy male subjects following a single oral dose.

Assessment of Single Doses of Oral Dexanabinol in Healthy Subjects

Assessment of Safety, Tolerability and Pharmacokinetics of Single Doses of Oral Dexanabinol in Healthy Subjects

Blood samples taken and analysed for the purposes of the identification and quantification of pharmacodynamic biomarkers pre-dose and at several points after dosing.

Safety and tolerability based on the number of participants with adverse events. Assessment and comparison to baseline of the following:

* Physical exam
* Safety bloods and urinalysis
* 12-lead ECG
* Vital signs

Pharmacokinetic parameters will be assessed in a blinded fashion at the end of each cohort, prior to dose escalation.

Single oral dose of dexanabinol

Dexanabinol: Oral formulation of dexanabinol

Single oral dose of dexanabinol

Dexanabinol: Oral formuulation of dexanabinol

Single oral dose of matching placebo

Placebo

Total

Age, Continuous

Sex: Female, Male

Healthy male subjects between 18 and 45 years of age with a body mass index between 18.0 and 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator.

Clinical Operations Manager

Safety and Tolerability Based on the Number of Participants With Adverse Events and Comparison of Baseline and Post Dose Parameters

Dose Level 2

Dose Level 3

Dose Level 4

Dose Level 5

Area Under the Curve of the Compound Dexanabinol (ETS2101) From Pre-dose up to 48 Hours Post Dose

Pharmacodynamic Biomarker Assessment

Single oral dose of dexanabinol at Dose Level 1

Dexanabinol: Oral formulation of dexanabinol

Single oral dose of dexanabinol at Dose level 2

Dexanabinol: Oral formulation of dexanabinol

Single oral dose of dexanabinol at Dose level 3

Dexanabinol: Oral formulation of dexanabinol

Single oral dose of dexanabinol at Dose level 4

Dexanabinol: Oral formulation of dexanabinol

Single oral dose of dexanabinol at Dose level 5

Dexanabinol: Oral formulation of dexanabinol

Overall Study

Anti-Infective Agents

Central Nervous System Depressants

Ethanol

Dexanabinol 2 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Dexanabinol 3 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Dexanabinol 6 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Dexanabinol 12 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Dexanabinol 15 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Dexanabinol 22 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Dexanabinol 30 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Dexanabinol 36 mg/kg formulated in cremophor/ethanol, administered once weekly intravenously (i.v.)

Patients will (initially) be given a slow intravenous (i.v.) infusion of Dexanabinol over 3 hours on Days 1, 8 and 15 of a three weekly (21 day) cycle.

Cremophor

Ruth Plummer, MD

Alan Anthoney, MD

Jeff Evans, MD

This study is a trial of Dexanabinol in patients with advanced solid tumours. The purposes of this protocol are to study different doses of the study drug to determine the maximum safe dose and to further understand the safety of the study drug; to understand what the body does to the study drug; to understand what the study drug does to the body and to measure any reduction in size of patients' cancer tumour(s).

Dexanabinol is a synthetic cannabinoid derivative with reduced psychotropic potential which was initially investigated as a neuroprotective agent. Because of its method of action however it is thought that it may have the effect of destroying cancer cells by reducing the level of control on networks that prevent cancer cells dying.

A Phase 1 Study of Dexanabinol in Patients With Advanced Solid Tumours

A Phase 1, Pharmacokinetically-Guided, Dose Escalation Study to Assess the Safety and Tolerability of Dexanabinol in Patients With Advanced Solid Tumours

Patients will be sequentially assigned to increasing doses of Dexanabinol, to establish the maximum tolerated dose (MTD) (highest dose it is safe to give patients) or alternatively the maximum administered dose (MAD).

3 patients will be enrolled to a cohort to assess each dose level. Dose escalation to a cohort of 3 new patients will occur when all patients in the previous cohort have completed the first cycle i.e. the first 3 doses followed by observation through to Day 22, and no DLT has occurred. Upon occurrence of the first DLT within a cohort, an additional 3 patients were to be added to that cohort. For a six patient cohort, all 6 patients were to have completed their first dexanabinol treatment cycle with no more than 1 DLT before dose escalation to the next cohort. If 2 or more DLTs occur in a cohort, the next lower dose level will be declared the MTD.

DLTs will be graded for severity based on the National Cancer Institute (NCI) Common Terminology Criteria version 4.03.

Geometric mean AUC of Dexanabinol (0-infinity) on Cycle 1 Day 1.

Mean Cmax of Dexanabinol on Cycle 1 Day 1

AEs will be graded according to the NCI CTCAE v4.03 for cancer clinical trials

Tumour response evaluation using RECIST 1.1. (Assessment by CT scan or MRI).

Geometric mean AUC of Dexanabinol (0-infinity) on Cycle 1 Day 8.

Geometric mean AUC of Cremophor (0-27hour) on Cycle 1 Day 1.

Geometric mean AUC of Cremophor (0-27hour) on Cycle 1 Day 8.

Mean Cmax of Dexanabinol on Cycle 1 Day 8

Dexanabinol 2 mg/kg

Dexanabinol 3 mg/kg

Dexanabinol 6 mg/kg

Dexanabinol 12 mg/kg

Dexanabinol 15 mg/kg

Dexanabinol 22 mg/kg

Dexanabinol 30 mg/kg

Dexanabinol 36 mg/kg

Dexanabinol Expansion Phase

Open label, dose escalation phase to assess tolerability and pharmacokinetics of dexanabinol in patients with advanced tumours

Dexanabinol Dose Escalation - Cohort 1

Dexanabinol Dose Escalation - Cohort 2

Dexanabinol Dose Escalation - Cohort 3

Dexanabinol Dose Escalation - Cohort 4

Dexanabinol Dose Escalation - Cohort 5

Dexanabinol Dose Escalation - Cohort 6

Dexanabinol Dose Escalation - Cohort 7

Dexanabinol Dose Escalation - Cohort 8

Open label, expansion phase to assess pharmacodynamics of dexanabinol in patients with advanced tumours at the MTD/MAD (30 mg/kg)

Age, Categorical

Gender

Patients will be sequentially assigned to increasing doses of Dexanabinol, to establish the MTD (highest dose it is safe to give patients) or alternatively the Maximum Administered Dose(MAD). DLT evaluation in 3 to 6 patients at end of 1 treatment cycle

Number of Patients Experiencing Dose Limiting Toxicity (DLT)

Concentrations of dexanabinol were not reported for some patients on Days 1 or 8 (including all patients in the 6 mg/kg arm) because the bioanalytical assay, in these instances, was not appropriately validated on the day of the assay. For the purposes of the PK analysis, the results from the expansion phase arm were combined with the 30 mg/kg arm.

Area Under Curve (AUC) of Dexanabinol on Cycle 1 Day 1

Maximum Concentration (Cmax) of Dexanabinol Cycle 1 Day 1

The numbers represent the total number of AEs per group. Refer to AE tables for specific information.

Number of Adverse Events (AEs)

Patients included in this analysis were from the 'Efficacy population', defined as those with a baseline and at least one post-baseline assessment of efficacy.

Progression Free Survival

Area Under Curve (AUC) of Dexanabinol on Cycle 1 Day 8

This analysis was performed on all patients who received study drug and for whom PK samples were obtained (the PK analysis population). For the purposes of the PK analysis, the results from the expansion phase arm were combined with the 30 mg/kg arm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours	NCT02423239	Hepatocellular ... Pancreatic Canc...	Dexanabinol Sorafenib Nab-paclitaxel Gemcitabine	18 Years -	e-Therapeutics PLC
Dexanabinol in Patients With Brain Cancer	NCT01654497	Brain Cancer	Dexanabinol	18 Years -	University of California, San Diego
Assessment of Single Doses of Oral Dexanabinol in Healthy Subjects	NCT02054754	Safety Tolerability Pharmacokinetic... Cancer	Dexanabinol Dos... Dexanabinol Dos... Dexanabinol Dos... Dexanabinol Dos... Dexanabinol Dos... Placebo	18 Years - 45 Years	e-Therapeutics PLC
A Study of Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours	NCT02423239	Hepatocellular ... Pancreatic Canc...	Dexanabinol Sorafenib Nab-paclitaxel Gemcitabine	18 Years -	e-Therapeutics PLC
A Phase 1 Study of Dexanabinol in Patients With Advanced Solid Tumours	NCT01489826	Solid Tumour	Dexanabinol Cremophor	18 Years -	e-Therapeutics PLC
Assessment of Single Doses of Oral Dexanabinol in Healthy Subjects	NCT02054754	Safety Tolerability Pharmacokinetic... Cancer	Dexanabinol Dos... Dexanabinol Dos... Dexanabinol Dos... Dexanabinol Dos... Dexanabinol Dos... Placebo	18 Years - 45 Years	e-Therapeutics PLC

Spots Global Cancer Trial Database for dexanabinol

Every month we try and update this database with for dexanabinol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for dexanabinol

Every month we try and update this database with for dexanabinol cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for dexanabinol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.