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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02423239
• Other study ID #: ETS2101-004
• Status: Active, not recruiting
• Phase: Phase 1
• First received: April 9, 2015
• Last updated: April 5, 2016
• Start date: April 2015
• Est. completion date: December 2016

Study information

• Verified date: April 2016
• Source: e-Therapeutics PLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Federal Institute for Drugs and Medical DevicesSpain: Agencia Española de Medicamentos y Productos SanitariosPoland: Main Pharmaceutical Inspectorate
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Dexanabinol
Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period
• Sorafenib
Patients will receive Sorafenib at a dose of 400 mg bid (oral administration)
• Nab-paclitaxel
Patients will receive Nab-paclitaxel at a dose of 125mg/m2 intravenous infusion
• Gemcitabine
Patients will receive Gemcitabine at a dose of 1000mg/m2 intravenous infusion

Locations

Country	Name	City	State
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	Universitätsklinikum Hamburg-Eppendorf II. Medizinischen Klinik Martinistr. 52	Hamburg
Germany	Klinikum der Ruhr-Universitaet Bochum, Medizinische Klinik III - Hämatologie/Onkologie Marien Hospital Herne Universitätsklinikum der Ruhr-Universität Bochum Hölkeskampring 40	Herne
Germany	Klinikum der Universität München, Universitätsklinikum Großhadern Medizinische Klinik und Poliklinik III AG Onkologie Marchioninistr. 15	München
Germany	UNIFONTIS Praxis fur Integrative Onkologie, Hoppe-Seyler-Straße 6,	Tübingen
Poland	Osrodek Medyczny SAMARYTANIN, ul. Kazimierza Puzaka 11	Opole
Poland	Wojewodzki Szpital Zespolony w Toruniu, ul. Sw. Józefa 53-59	Torun
Spain	START MADRID-FJD, Hospital Fundación Jiménez Díaz, Av Reyes Católicos 2, Floor 1 28040	Madrid
Spain	Hospital Universitario Virgen de la Victoria, Servicio de Oncología Médica Campus de Teatinos,	Málaga	Malaga
Spain	Hospital Universitario Virgen del Rocio, Hospital Universitario Virgen del Rocío Oncología Médica Avda. Manuel Siurot,	Sevilla
United Kingdom	Beatson West of Scotland Cancer Centre, 1053 Great Western Rd,	Glasgow
United Kingdom	St James's Hospital, Cancer Research UK Clinical Centre/Section of Oncology, Beckett St,	Leeds
United Kingdom	Freeman Hospital, Sir Bobby Robson Cancer Trials Research Centre, Freeman Road, High Heaton,	Newcastle upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
e-Therapeutics PLC

Countries where clinical trial is conducted

Germany,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Tumour response ( RECIST 1.1, assessment by CT or MRI)	Tumour response evaluation using 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	No