Clinical trial NCT01489826: A Phase 1 Study of Dexanabinol in Patients With Advanced Solid Tumours
Official title: A Phase 1, Pharmacokinetically-Guided, Dose Escalation Study to Assess the Safety and Tolerability of Dexanabinol in Patients With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumour
Keywords: Cancer
Lead sponsor: e-Therapeutics PLC
Sponsor class: INDUSTRY
First posted: 2011-12-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.
4. 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.
5. 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).
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;
   * 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).
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.

Primary outcomes:
measure: Number of Patients Experiencing Dose Limiting Toxicity (DLT)
timeFrame: Each patient will be followed for 22 days
Secondary outcomes:
measure: Area Under Curve (AUC) of Dexanabinol on Cycle 1 Day 1
timeFrame: 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.
measure: Maximum Concentration (Cmax) of Dexanabinol Cycle 1 Day 1
timeFrame: 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.
measure: Number of Adverse Events (AEs)
timeFrame: 30 +/-3 days from the end of the last infusion
measure: Progression Free Survival
timeFrame: At Screening and after every 2 cycles of treatment (+/-1 week)
measure: Area Under Curve (AUC) of Dexanabinol on Cycle 1 Day 8
timeFrame: 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.
measure: Area Under Curve (AUC) of Cremophor on Cycle 1 Day 1
timeFrame: 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.
measure: Area Under Curve (AUC) of Cremophor on Cycle 1 Day 8
timeFrame: 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.
measure: Maximum Concentration (Cmax) of Dexanabinol Cycle 1 Day 8
timeFrame: Cycle1 - 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.
measure: Maximum Concentration (Cmax) of Cremophor Cycle 1 Day 1
timeFrame: 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.
measure: Maximum Concentration (Cmax) of Cremophor Cycle 1 Day 8
timeFrame: Cycle1 - 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.
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Care, Freeman Hospital, Newcastle-upon-Tyne, UK
state: Tyne and Wear
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre,
Study officials:
affiliation: Northern Centre for Cancer Care, Freeman Hospital, Newcastle-upon-Tyne, UK
name: Ruth Plummer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leeds Cancer Centre at St. James's University Hospital
name: Alan Anthoney, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow
name: Jeff Evans, MD
role: PRINCIPAL_INVESTIGATOR
References: