Clinical trial NCT02423239: A Study of Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours
Official title: A Phase 1b Study to Assess the Safety and Anti-tumour Activity of Dexanabinol Monotherapy and Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Pancreatic Cancer
Lead sponsor: e-Therapeutics PLC
Sponsor class: INDUSTRY
First posted: 2015-04-22
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a trial of dexanabinol in patients with advanced tumours. The purposes of the protocol are to study different doses of the study drug to determine the maximum safe dose of the drug given in combination with standard chemotherapies and to further understand the safety of the study drug and to measure any reduction in size of patients' cancer tumour(s).

Dexanabinol is a synthetic cannabinoid which has previously undergone clinical trials for traumatic brain injury (TBI) and in subjects undergoing coronary artery bypass surgery. Currently dexanabinol is under investigation for potential anti-tumour activity in patients with advanced tumours.


Eligibility criteria: Inclusion Criteria

1. (i) Parts 1 and 2b (dexanabinol combination): Patients with selected histologically, cytologically or radiologically confirmed tumours that are advanced, metastatic and/or progressive, and eligible for 1st line chemotherapy.

   * HCC only: patient with Child-Pugh A stage.
   * Pancreatic cancer only: patients diagnosed with adenocarcinoma (i.e. pancreatic cancer patients with islet cell neuroplasms are excluded).

   (ii) Part 2a (dexanabinol monotherapy): Patients with histologically, cytologically or radioloigically confirmed tumours that are advanced, metastatic and/or progressive, for whom there is no effective standard therapy available.
   * Pancreatic cancer only: patients diagnosed with adenocarinoma (i.e. pancreatic cancer patients with islet cell neuroplasms are excluded).
2. Adults patients defined by age ≥ 18 years.
3. Eastern Collaborative Oncology Group (ECOG) Performance Status (PS) or 0 or 1.
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.
5. (i) Parts 1 and 2b: Measureable disease assessed by appropriate method for each tumour type e.g. RECIST 1.1 (Eisenhauer, et al. 2009).

   (ii) Part 2a: Evaluable disease, either measureable on imaging, or with informative tumour marker(s).
6. Laboratory values at Screening:

   * Absolute neutrophil count ≥ 1.5 x 109L;
   * Platelets ≥ 100 x 109/L;
   * Total bilirubin; in 1st line pancreatic cancer (part 1 and 2b) ≤1.25 times the upper limit of normal (ULN); all other tumour types and settings except HCC ≤1.5 times ULN; in HCC ≤5 times the ULN
   * AST (SGOT) ≤2.5 times the ULN (when there is no liver tumour involvement) up to

     * 5 times the ULN (in patients with liver tumour involvement);
   * ALT (SGPT) ≤2.5 times the ULN (when there is no liver tumour involvement) up to

     * 5 times the ULN (in patients with liver tumour involvement);
   * Estimated GFR of \>50 mL/min (based on the Wright formula (Wright, et al. 2001 ); and
   * Negative hCG test in women of childbearing potential
7. Have a life expectancy of \>3 months.
8. 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.
9. 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. Known brain metastases.
4. (i) Parts 1 and 2b (dexanabinol combination): Prior systemic chemotherapy.

   (ii) Part 2a (dexanabinol monotherapy): Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Cycle 1, Day 1 for solid tumours (with the exception of hydroxyurea, which must be discontinued at least 24 hours prior to Cycle 1, Day 1). Localised palliative radiotherapy is permitted for symptom control.
5. Major surgery within 4 weeks prior to Cycle 1, Day 1; bone marrow transplant within 100 days prior to Cycle 1, Day 1.
6. Known human immunodeficiency virus positivity.
7. Active hepatitis B or C or other active liver disease (other than malignancy) (applies to all tumours types enrolled except HCC).
8. Use of any investigational agents within 4 weeks of Cycle 1, Day 1.
9. Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.
10. 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: Maximum Tolerated Dose (MTD) of dexanabinol given in combination with standard chemotherapies
timeFrame: For 29 days from the day of first dose
measure: Number of adverse events (AEs) in patients receiving dexanabinol monotherapy
timeFrame: From start of dosing until 30 days ± 3 days post last dose of dexanbinol
measure: Number of adverse events (AEs) in patients receiving dexanabinol in combination with standard chemotherapies
timeFrame: From start of dosing until 30 days ± 3 days post last dose of IMP
Secondary outcomes:
measure: Area under curve (AUC) of dexanabinol and (where applicable) combination chemotherapy
timeFrame: Cycle 1 Day 1 and Day 8 pre-dose (0h); 1, 2, 3h (i.e. immediately prior to end infusion) post start of infusion; 5, 10, 15, 30 min post-end infusion; 1, 2, 3, 4, 6, 8, 10 and 24h post-end infusion; day 15 immediately prior to and at end of IMP infusion
measure: Maximum concentration (Cmax) of dexanabinol and (where applicable) combination chemotherapy
timeFrame: Cycle 1 Day 1 and Day 8 pre-dose (0h); 1, 2, 3h (i.e. immediately prior to end infusion) post start of infusion; 5, 10, 15, 30 min post-end infusion; 1, 2, 3, 4, 6, 8, 10 and 24h post-end infusion day 15 immediately prior to and at end of IMP infusion
measure: Minimum concentration (Cmin) of dexanabinol and (where applicable) combination chemotherapy
timeFrame: Cycle 1 Day 1 and Day 8 pre-dose (0h); 1, 2, 3h (i.e. immediately prior to end infusion) post start of infusion; 5, 10, 15, 30 min post-end infusion; 1, 2, 3, 4, 6, 8, 10 and 24h post-end infusion day 15 immediately prior to and at end of IMP infusion
measure: Tumour response ( RECIST 1.1, assessment by CT or MRI)
timeFrame: Participants will be followed until objective disease progression as per the RECIST v1.1 criteria, an expected average of four months
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University Hospital Bonn, Study Center Bonn (SZB) Clinical Study Core Unit Institute of Clinical Chemistry and Clinical Pharmacology University Hospital Bonn, Sigmund-Freud-Str. 25
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf II. Medizinischen Klinik Martinistr. 52
city: Herne
country: Germany
facility: Klinikum der Ruhr-Universitaet Bochum, Medizinische Klinik III - Hämatologie/Onkologie Marien Hospital Herne Universitätsklinikum der Ruhr-Universität Bochum Hölkeskampring 40
city: München
country: Germany
facility: Klinikum der Universität München, Universitätsklinikum Großhadern Medizinische Klinik und Poliklinik III AG Onkologie Marchioninistr. 15
city: Tübingen
country: Germany
facility: UNIFONTIS Praxis fur Integrative Onkologie, Hoppe-Seyler-Straße 6,
city: Opole
country: Poland
facility: Osrodek Medyczny SAMARYTANIN, ul. Kazimierza Pużaka 11
city: Toruń
country: Poland
facility: Wojewodzki Szpital Zespolony w Toruniu, ul. Św. Józefa 53-59
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria, Servicio de Oncología Médica Campus de Teatinos,
state: Malaga
city: Madrid
country: Spain
facility: START MADRID-FJD, Hospital Fundación Jiménez Díaz, Av Reyes Católicos 2, Floor 1 28040
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio, Hospital Universitario Virgen del Rocío Oncología Médica Avda. Manuel Siurot,
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre, 1053 Great Western Rd,
city: Leeds
country: United Kingdom
facility: St James's Hospital, Cancer Research UK Clinical Centre/Section of Oncology, Beckett St,
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital, Sir Bobby Robson Cancer Trials Research Centre, Freeman Road, High Heaton,
Study officials:
References: