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

NCT02423239 | Unknown Phase 1

• 1 other identifier: ETS2101-004
• Study Type: interventional
• Target: 112
• Locations: 4 countries
• Sites: 13

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.

Conditions

Hepatocellular Carcinoma; Pancreatic Cancer

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) of dexanabinol given in combination with standard chemotherapies

  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.

  For 29 days from the day of first dose

• Number of adverse events (AEs) in patients receiving dexanabinol monotherapy

  AEs will be graded according to the NCI CTCAE v4.03 for cancer clinical trials.

  From start of dosing until 30 days ± 3 days post last dose of dexanbinol

• Number of adverse events (AEs) in patients receiving dexanabinol in combination with standard chemotherapies

  AEs will be graded according to the NCI CTCAE v4.03 for cancer clinical trials.

  From start of dosing until 30 days ± 3 days post last dose of IMP

Secondary Outcomes (4)

• Area under curve (AUC) of dexanabinol and (where applicable) combination chemotherapy

  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

• Maximum concentration (Cmax) of dexanabinol and (where applicable) combination chemotherapy

  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

• Minimum concentration (Cmin) of dexanabinol and (where applicable) combination chemotherapy

  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

• Tumour response ( RECIST 1.1, assessment by CT or MRI)

  Participants will be followed until objective disease progression as per the RECIST v1.1 criteria, an expected average of four months

Study Arms (3)

Relapsed or refractory advanced tumours

EXPERIMENTAL

Patients with selected relapsed or refractory tumour types to receive single agent dexanabinol.

Drug: Dexanabinol

Newly diagnosed hepatocellular carcinoma

EXPERIMENTAL

Patients with hepatocellular carcinoma to receive dexanabinol in combination with standard chemotherapy.

Drug: Dexanabinol; Drug: Sorafenib

Newly diagnosed pancreatic cancer

EXPERIMENTAL

Patients with pancreatic cancer to receive dexanabinol in combination with standard chemotherapy

Drug: Dexanabinol; Drug: Nab-paclitaxel; Drug: Gemcitabine

Interventions

Dexanabinol DRUG

Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period

Also known as: ETS2101, HU-211

Newly diagnosed hepatocellular carcinoma; Newly diagnosed pancreatic cancer; Relapsed or refractory advanced tumours

Sorafenib DRUG

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

Newly diagnosed hepatocellular carcinoma

Nab-paclitaxel DRUG

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

Newly diagnosed pancreatic cancer

Gemcitabine DRUG

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

Newly diagnosed pancreatic cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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).
• Adults patients defined by age ≥ 18 years.
• Eastern Collaborative Oncology Group (ECOG) Performance Status (PS) or 0 or 1.
• 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.
• (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).
• 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

You may not qualify if:

• Patient is pregnant or breast feeding.
• History of clinically significant cardiac condition, including ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months of Cycle 1, Day 1.
• Known brain metastases.
• (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.
• Major surgery within 4 weeks prior to Cycle 1, Day 1; bone marrow transplant within 100 days prior to Cycle 1, Day 1.
• Known human immunodeficiency virus positivity.
• Active hepatitis B or C or other active liver disease (other than malignancy) (applies to all tumours types enrolled except HCC).
• Use of any investigational agents within 4 weeks of Cycle 1, Day 1.
• Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.
• 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.

Sponsors & Collaborators

• e-Therapeutics PLC: lead

Study Sites (13)

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, D-53127, Germany

Location

Universitätsklinikum Hamburg-Eppendorf II. Medizinischen Klinik Martinistr. 52

Hamburg, 20246, Germany

Location

Klinikum der Ruhr-Universitaet Bochum, Medizinische Klinik III - Hämatologie/Onkologie Marien Hospital Herne Universitätsklinikum der Ruhr-Universität Bochum Hölkeskampring 40

Herne, 44625, Germany

Location

Klinikum der Universität München, Universitätsklinikum Großhadern Medizinische Klinik und Poliklinik III AG Onkologie Marchioninistr. 15

München, 81377, Germany

Location

UNIFONTIS Praxis fur Integrative Onkologie, Hoppe-Seyler-Straße 6,

Tübingen, 72076, Germany

Location

Osrodek Medyczny SAMARYTANIN, ul. Kazimierza Pużaka 11

Opole, 45-272, Poland

Location

Wojewodzki Szpital Zespolony w Toruniu, ul. Św. Józefa 53-59

Torun, 87-100, Poland

Location

Hospital Universitario Virgen de la Victoria, Servicio de Oncología Médica Campus de Teatinos,

Málaga, Malaga, 29010, Spain

Location

START MADRID-FJD, Hospital Fundación Jiménez Díaz, Av Reyes Católicos 2, Floor 1 28040

Madrid, 28040, Spain

Location

Hospital Universitario Virgen del Rocio, Hospital Universitario Virgen del Rocío Oncología Médica Avda. Manuel Siurot,

Seville, 41013, Spain

Location

Beatson West of Scotland Cancer Centre, 1053 Great Western Rd,

Glasgow, G12 0YN, United Kingdom

Location

St James's Hospital, Cancer Research UK Clinical Centre/Section of Oncology, Beckett St,

Leeds, LS9 7TF, United Kingdom

Location

Freeman Hospital, Sir Bobby Robson Cancer Trials Research Centre, Freeman Road, High Heaton,

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Pancreatic Neoplasms

Interventions

HU 211; Sorafenib; 130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2015
• First Posted: April 22, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 6, 2016

Record last verified: 2016-04

Locations

GB (3); DE (5); ES (3); PL (2)