A Phase 1 Study of Dexanabinol in Patients With Advanced Solid Tumours
Condition: Solid Tumour
MeSH terms: Neoplasms
Intervention: Dexanabinol; Cremophor
Intervention description: 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.; Drug vehicle.
Intervention MeSH terms: HU 211
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer

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.