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

NCT01489826 | Completed Phase 1 Results DMC

• 1 other identifier: ETS2101-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Solid Tumour

Keywords

Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients Experiencing Dose Limiting Toxicity (DLT)

  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.

  Each patient will be followed for 22 days

Secondary Outcomes (10)

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

  Cycle 1- Day 1: pre-dose (0h); 1, 2, 3 h post start of infusion; 5, 10, 15, 30 min post-end infusion; 1, 2, 3, 4, 6, 8, 10 and 24 h post-end infusion.

• Maximum Concentration (Cmax) of Dexanabinol Cycle 1 Day 1

  Cycle1 - Day 1: pre-dose (0h); 1, 2, 3 h post start of infusion; 5, 10, 15, 30 min post-end infusion; 1, 2, 3, 4, 6, 8, 10 and 24 h post-end infusion.

• Number of Adverse Events (AEs)

  30 +/-3 days from the end of the last infusion

• Progression Free Survival

  At Screening and after every 2 cycles of treatment (+/-1 week)

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

  Cycle 1- Day 8: pre-dose (0h); 1, 2, 3 h post start of infusion; 5, 10, 15, 30 min post-end infusion; 1, 2, 3, 4, 6, 8, 10 and 24 h post-end infusion.

Study Arms (9)

Dexanabinol 2 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol 3 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol 6 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol 12 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol 15 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol 22 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol 30 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol 36 mg/kg

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Dexanabinol Expansion Phase

EXPERIMENTAL

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

Drug: Dexanabinol; Other: Cremophor

Interventions

Dexanabinol DRUG

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.

Also known as: ETS2101, HU-211

Dexanabinol 12 mg/kg; Dexanabinol 15 mg/kg; Dexanabinol 2 mg/kg; Dexanabinol 22 mg/kg; Dexanabinol 3 mg/kg; Dexanabinol 30 mg/kg; Dexanabinol 36 mg/kg; Dexanabinol 6 mg/kg; Dexanabinol Expansion Phase

Cremophor OTHER

Drug vehicle.

Dexanabinol 12 mg/kg; Dexanabinol 15 mg/kg; Dexanabinol 2 mg/kg; Dexanabinol 22 mg/kg; Dexanabinol 3 mg/kg; Dexanabinol 30 mg/kg; Dexanabinol 36 mg/kg; Dexanabinol 6 mg/kg; Dexanabinol Expansion Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients defined by age ≥18 years.
• Patients with histologically or cytologically confirmed solid tumours that are advanced, metastatic and or progressive, for whom there is no effective standard therapy available.
• Eastern Collaborative Oncology Group (ECOG) Performance Status of ≤2.
• Any acute or chronic adverse effects of prior chemotherapy or radiotherapy have resolved to \< Grade 2 as determined by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, with the exception of alopecia.
• Evaluable disease, either measurable on imaging, or with informative tumour marker(s), as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Eisenhauer, et al. 2009).
• Laboratory values at Screening:
• Absolute neutrophil count ≥1.5 x 109/L;
• Platelets ≥100 x 109/L;
• Total bilirubin \<1.5 times the upper limit of normal;
• Aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal;
• Alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal;
• Estimated glomerular filtration rate (GFR) of \>50 mL/min (based on the Wright formula (Wright, et al. 2001); and
• Negative human chorionic gonadotropin (hCG) test in women of childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12 months prior to study entry). Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control (e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study and for 1 month after final administration of Dexanabinol, or the patient must be surgically sterile (with documentation in the patient's medical records).
• If there is a history of treated brain metastases, these must have been clinically stable for ≥4 weeks prior to enrollment.
• Have a life expectancy of \>3 months.

You may not qualify if:

• Patient is pregnant or breast feeding.
• History of clinically significant cardiac condition, including ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months of Cycle 1, Day 1.
• Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control.
• Major surgery within 6 weeks prior to Cycle 1, Day 1.
• Known human immunodeficiency virus positivity.
• Active hepatitis B or C or other active liver disease (other than malignancy).
• Use of any investigational agents within 4 weeks of Cycle 1, Day 1.
• Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.
• History of significant chronic or recurrent infections requiring treatment or any uncontrolled intercurrent illness that would jeopardize patient safety, interfere with the objectives of the protocol, or limit patient compliance with study requirements, as determined by the Investigator.

Sponsors & Collaborators

• e-Therapeutics PLC: lead

Study Sites (3)

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Northern Centre for Cancer Care, Freeman Hospital, Newcastle-upon-Tyne, UK

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

The Beatson West of Scotland Cancer Centre,

Glasgow, G12 0YN, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

HU 211; cremophor

Results Point of Contact

• Title: Clinical Operations Manager
• Organization: e-Therapeutics plc

contact@etherapeutics.co.uk

+44 1993 880000

Study Officials

• Ruth Plummer, MD

  Northern Centre for Cancer Care, Freeman Hospital, Newcastle-upon-Tyne, UK

  PRINCIPAL INVESTIGATOR

• Alan Anthoney, MD

  Leeds Cancer Centre at St. James's University Hospital

  PRINCIPAL INVESTIGATOR

• Jeff Evans, MD

  The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2011
• First Posted: December 12, 2011
• Study Start: January 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: February 9, 2017
• Results First Posted: October 18, 2016

Record last verified: 2016-10

Locations

GB (3)