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

Solid Tumour Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01489826
• Other study ID #: ETS2101-001
• Status: Completed
• Phase: Phase 1
• First received: December 7, 2011
• Last updated: August 3, 2015
• Start date: January 2012

Study information

• Verified date: August 2015
• Source: e-Therapeutics PLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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 nonpsychotropic cannabinoid derivative which was initially developed as a neuroprotective agent due to its antiinflammatory activity. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult patients defined by age =18 years.

2. Patients with histologically or cytologically confirmed solid tumours that are advanced, metastatic and or progressive, for whom there is no effective standard therapy available.

3. Eastern Collaborative Oncology Group (ECOG) Performance Status of =2 (Appendix A).

4. Any acute or chronic adverse effects of prior chemotherapy or radiotherapy have resolved to < Grade 2 as determined by CTCAE v4.03 criteria, with the exception of alopecia (Appendix B).

5. Evaluable disease, either measurable on imaging, or with informative tumour marker(s), as assessed by RECIST 1.1 (Eisenhauer, et al. 2009).

6. 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;

• AST (SGOT) =2.5 times the upper limit of normal;

• ALT (SGPT) =2.5 times the upper limit of normal;

• Estimated GFR of >50 mL/min (based on the Wright formula (Wright, et al. 2001); and

• Negative 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).

7. If there is a history of treated brain metastases, these must have been clinically stable for =4 weeks prior to enrollment.

8. Have a life expectancy of >3 months.

9. Ability to give written, informed consent prior to any study-specific Screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.

10. Be willing and able to comply with the study protocol procedures.

Exclusion Criteria:

1. Patient is pregnant or breast feeding.

2. History of clinically significant cardiac condition, including ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months of Cycle 1, Day 1.

3. 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.

4. Major surgery within 6 weeks prior to Cycle 1, Day 1.

5. Known human immunodeficiency virus positivity.

6. Active hepatitis B or C or other active liver disease (other than malignancy).

7. Use of any investigational agents within 4 weeks of Cycle 1, Day 1.

8. Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.

9. 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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumour

Intervention

Drug:
• Dexanabinol
Patients will (initially) be given a slow infusion (IV) of Dexanabinol over 3 hours on Days 1, 8 and 15 of a three weekly (21 day) cycle

Locations

Country	Name	City	State
United Kingdom	The Beatson West of Scotland Cancer Centre,	Glasgow
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Northern Centre for Cancer Care, Freeman Hospital, Newcastle-upon-Tyne, UK	Newcastle-upon-Tyne	Tyne and Wear

Sponsors (1)

Lead Sponsor	Collaborator
e-Therapeutics PLC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	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).; 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 Dose Limiting Toxicity (DLT) has occurred.; DLTs will be graded for severity based on the NCI Common Terminology Criteria version 4.03	Each patient will be followed for 22 days	Yes
Secondary	Area Under Curve (AUC) of Dexanabinol and Cremophor		Cycle1- Day 1 and 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. Day 15: immediately prior to infusion and at the end of infusion.	No
Secondary	Maximum Concentration (Cmax) of Dexanabinol and Cremophor		Cycle1 - Day 1 and 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. Day 15: immediately prior to infusion and at the end of infusion.	No
Secondary	Minimum Concentration (Cmin) of Dexanabinol and Cremophor		Cycle 1 - Day 1 and 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. Day 15: immediately prior to infusion and at the end of infusion.	No
Secondary	Number of adverse events (AEs)	AEs will be graded according to the NCI CTCAE v4.03 for cancer clinical trials	30 +/-3 days from the end of the last infusion	Yes
Secondary	Tumour response	Tumour response evaluation using RECIST 1.1. (Assessment by CT scan or MRI). An additional scan will be performed to confirm a Complete Response (CR) or Partial Response (PR). Tumour markers may be evaluated where appropriate	At Screening and after every 2 cycles of treatment (+/-1 week)	No