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A Study of Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours

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ClinicalTrials.gov Identifier: NCT02423239
Recruitment Status : Unknown
Verified April 2016 by e-Therapeutics PLC.
Recruitment status was:  Active, not recruiting
First Posted : April 22, 2015
Last Update Posted : April 6, 2016
Sponsor:
Information provided by (Responsible Party):
e-Therapeutics PLC

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.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Pancreatic Cancer Drug: Dexanabinol Drug: Sorafenib Drug: Nab-paclitaxel Drug: Gemcitabine Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : April 2015
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016

Arm Intervention/treatment
Experimental: Relapsed or refractory advanced tumours
Patients with selected relapsed or refractory tumour types to receive single agent dexanabinol.
Drug: Dexanabinol
Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period
Other Names:
  • ETS2101
  • HU-211

Experimental: Newly diagnosed hepatocellular carcinoma
Patients with hepatocellular carcinoma to receive dexanabinol in combination with standard chemotherapy.
Drug: Dexanabinol
Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period
Other Names:
  • ETS2101
  • HU-211

Drug: Sorafenib
Patients will receive Sorafenib at a dose of 400 mg bid (oral administration)

Experimental: Newly diagnosed pancreatic cancer
Patients with pancreatic cancer to receive dexanabinol in combination with standard chemotherapy
Drug: Dexanabinol
Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period
Other Names:
  • ETS2101
  • HU-211

Drug: Nab-paclitaxel
Patients will receive Nab-paclitaxel at a dose of 125mg/m2 intravenous infusion

Drug: Gemcitabine
Patients will receive Gemcitabine at a dose of 1000mg/m2 intravenous infusion




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of dexanabinol given in combination with standard chemotherapies [ Time Frame: For 29 days from the day of first dose ]
    Patients will be sequentially assigned to increasing doses of dexanabinol to establish the MTD (or 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 four doses followed by observation through to day 29 and no dose limiting toxicity (DLT) has occurred.

  2. Number of adverse events (AEs) in patients receiving dexanabinol monotherapy [ Time Frame: From start of dosing until 30 days ± 3 days post last dose of dexanbinol ]
    AEs will be graded according to the NCI CTCAE v4.03 for cancer clinical trials.

  3. Number of adverse events (AEs) in patients receiving dexanabinol in combination with standard chemotherapies [ Time Frame: From start of dosing until 30 days ± 3 days post last dose of IMP ]
    AEs will be graded according to the NCI CTCAE v4.03 for cancer clinical trials.


Secondary Outcome Measures :
  1. Area under curve (AUC) of dexanabinol and (where applicable) combination chemotherapy [ Time Frame: 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 ]
  2. Maximum concentration (Cmax) of dexanabinol and (where applicable) combination chemotherapy [ Time Frame: 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 ]
  3. Minimum concentration (Cmin) of dexanabinol and (where applicable) combination chemotherapy [ Time Frame: 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 ]
  4. Tumour response ( RECIST 1.1, assessment by CT or MRI) [ Time Frame: Participants will be followed until objective disease progression as per the RECIST v1.1 criteria, an expected average of four months ]
    Tumour response evaluation using RECIST 1.1 (assessment by CT or MRI).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423239


Locations
Germany
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
Bonn, Germany, D-53127
Universitätsklinikum Hamburg-Eppendorf II. Medizinischen Klinik Martinistr. 52
Hamburg, Germany, 20246
Klinikum der Ruhr-Universitaet Bochum, Medizinische Klinik III - Hämatologie/Onkologie Marien Hospital Herne Universitätsklinikum der Ruhr-Universität Bochum Hölkeskampring 40
Herne, Germany, 44625
Klinikum der Universität München, Universitätsklinikum Großhadern Medizinische Klinik und Poliklinik III AG Onkologie Marchioninistr. 15
München, Germany, 81377
UNIFONTIS Praxis fur Integrative Onkologie, Hoppe-Seyler-Straße 6,
Tübingen, Germany, 72076
Poland
Osrodek Medyczny SAMARYTANIN, ul. Kazimierza Pużaka 11
Opole, Poland, 45-272
Wojewodzki Szpital Zespolony w Toruniu, ul. Św. Józefa 53-59
Toruń, Poland, 87-100
Spain
Hospital Universitario Virgen de la Victoria, Servicio de Oncología Médica Campus de Teatinos,
Málaga, Malaga, Spain, 29010
START MADRID-FJD, Hospital Fundación Jiménez Díaz, Av Reyes Católicos 2, Floor 1 28040
Madrid, Spain, 28040
Hospital Universitario Virgen del Rocio, Hospital Universitario Virgen del Rocío Oncología Médica Avda. Manuel Siurot,
Sevilla, Spain, 41013
United Kingdom
Beatson West of Scotland Cancer Centre, 1053 Great Western Rd,
Glasgow, United Kingdom, G12 0YN
St James's Hospital, Cancer Research UK Clinical Centre/Section of Oncology, Beckett St,
Leeds, United Kingdom, LS9 7TF
Freeman Hospital, Sir Bobby Robson Cancer Trials Research Centre, Freeman Road, High Heaton,
Newcastle upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
e-Therapeutics PLC

Responsible Party: e-Therapeutics PLC
ClinicalTrials.gov Identifier: NCT02423239     History of Changes
Other Study ID Numbers: ETS2101-004
First Posted: April 22, 2015    Key Record Dates
Last Update Posted: April 6, 2016
Last Verified: April 2016

Additional relevant MeSH terms:
Pancreatic Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Liver Diseases
Paclitaxel
Gemcitabine
Sorafenib
Albumin-Bound Paclitaxel
HU 211
Dronabinol
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents