Anti-Infective Agents

Central Nervous System Depressants

All Drugs and Chemicals

Anti-Arrhythmia Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Ethanol

HU 211

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

Protective Agents

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.

Dexanabinol

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

e-Therapeutics PLC

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)

Total

Age, Categorical

Age, Continuous

Gender

Clinical Operations Manager

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.

Spots Global Cancer Trial Database for A Phase 1 Study of Dexanabinol in Patients With Advanced Solid Tumours

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial