Hepatocellular CarcinomaPhase 1NCT02423239
A Study of Dexanabinol in Combination With Chemotherapy in Patients With Advanced Tumours
A Phase 1 study testing Dexanabinol, Sorafenib and Nab-paclitaxel in people with Hepatocellular Carcinoma and Pancreatic Cancer, run by e-Therapeutics PLC at 13 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Pancreatic Cancer
- What is being tested?
- Dexanabinol, Sorafenib and Nab-paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 13 sitesin 4 countries
- Study dates
- Apr 2015to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- (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).
- 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.
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- 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).
- 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
- 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
- Have a life expectancy of >3 months.
- 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.
- Be willing and able to comply with the study protocol procedures.
Who cannot join
- 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.
- 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.
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- 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.
Trial locations and contacts
13 sites in 4 countries.
13 sites in 4 countries
Germany5 sites
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
Universitätsklinikum Hamburg-Eppendorf II. Medizinischen Klinik Martinistr. 52
Hamburg, 20246
Klinikum der Ruhr-Universitaet Bochum, Medizinische Klinik III - Hämatologie/Onkologie Marien Hospital Herne Universitätsklinikum der Ruhr-Universität Bochum Hölkeskampring 40
Herne, 44625
Klinikum der Universität München, Universitätsklinikum Großhadern Medizinische Klinik und Poliklinik III AG Onkologie Marchioninistr. 15
München, 81377
UNIFONTIS Praxis fur Integrative Onkologie, Hoppe-Seyler-Straße 6,
Tübingen, 72076
Spain3 sites
START MADRID-FJD, Hospital Fundación Jiménez Díaz, Av Reyes Católicos 2, Floor 1 28040
Madrid, 28040
Hospital Universitario Virgen de la Victoria, Servicio de Oncología Médica Campus de Teatinos,
Málaga, Malaga, 29010
Hospital Universitario Virgen del Rocio, Hospital Universitario Virgen del Rocío Oncología Médica Avda. Manuel Siurot,
Seville, 41013
United Kingdom3 sites
Beatson West of Scotland Cancer Centre, 1053 Great Western Rd,
Glasgow, G12 0YN
St James's Hospital, Cancer Research UK Clinical Centre/Section of Oncology, Beckett St,
Leeds, LS9 7TF
Freeman Hospital, Sir Bobby Robson Cancer Trials Research Centre, Freeman Road, High Heaton,
Newcastle upon Tyne, NE7 7DN
Poland2 sites
Osrodek Medyczny SAMARYTANIN, ul. Kazimierza Pużaka 11
Opole, 45-272
Wojewodzki Szpital Zespolony w Toruniu, ul. Św. Józefa 53-59
Torun, 87-100
About this study
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
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
- Being tested
- Dexanabinol, Sorafenib, Nab-paclitaxel, Gemcitabine
- Medical subject headings
- Carcinoma, Hepatocellular, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexanabinolDrug
Also called ETS2101, HU-211
Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period
SorafenibDrug
Patients will receive Sorafenib at a dose of 400 mg bid (oral administration)
Nab-paclitaxelDrug
Patients will receive Nab-paclitaxel at a dose of 125mg/m2 intravenous infusion
GemcitabineDrug
Patients will receive Gemcitabine at a dose of 1000mg/m2 intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Relapsed or refractory advanced tumours | Experimental | Patients with selected relapsed or refractory tumour types to receive single agent dexanabinol. Receives: Drug: Dexanabinol |
| Newly diagnosed hepatocellular carcinoma | Experimental | Patients with hepatocellular carcinoma to receive dexanabinol in combination with standard chemotherapy. Receives: Drug: Dexanabinol; Drug: Sorafenib |
| Newly diagnosed pancreatic cancer | Experimental | Patients with pancreatic cancer to receive dexanabinol in combination with standard chemotherapy Receives: Drug: Dexanabinol; Drug: Nab-paclitaxel; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Tumour response evaluation using RECIST 1.1 (assessment by CT or MRI).
Measured: Participants will be followed until objective disease progression as per the RECIST v1.1 criteria, an expected average of four months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- e-Therapeutics PLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423239
- Sponsor's protocol ID
- ETS2101-004
- Status last verified
- Apr 2016
- First submitted
- 9 Apr 2015
- Last updated
- 6 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02423239
- Acronym / sponsor ID
- ETS2101-004
- Conditions
- Hepatocellular Carcinoma, Pancreatic Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- e-Therapeutics PLCIndustry (pharma, biotech, devices)
- Study start
- Apr 2015
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 22 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Relapsed or refractory advanced tumours | Experimental | Drug: DexanabinolPatients with selected relapsed or refractory tumour types to receive single agent dexanabinol. |
| Newly diagnosed hepatocellular carcinoma | Experimental | Drug: Dexanabinol, Drug: SorafenibPatients with hepatocellular carcinoma to receive dexanabinol in combination with standard chemotherapy. |
| Newly diagnosed pancreatic cancer | Experimental | Drug: Dexanabinol, Drug: Nab-paclitaxel, Drug: GemcitabinePatients with pancreatic cancer to receive dexanabinol in combination with standard chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- (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.
- 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).
Key exclusion criteria (11 listed)
- 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.
- Major surgery within 4 weeks prior to Cycle 1, Day 1; bone marrow transplant within 100 days prior to Cycle 1, Day 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexanabinolAlso: ETS2101, HU-211Patients will receive dexanabinol given once a week, as a slow intravenous infusion (i.v.) over a 3 hour period | Drug | Newly diagnosed hepatocellular carcinoma, Newly diagnosed pancreatic cancer, Relapsed or refractory advanced tumours |
| SorafenibPatients will receive Sorafenib at a dose of 400 mg bid (oral administration) | Drug | Newly diagnosed hepatocellular carcinoma |
| Nab-paclitaxelPatients will receive Nab-paclitaxel at a dose of 125mg/m2 intravenous infusion | Drug | Newly diagnosed pancreatic cancer |
| GemcitabinePatients will receive Gemcitabine at a dose of 1000mg/m2 intravenous infusion | Drug | Newly diagnosed pancreatic cancer |
Primary outcome
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.
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.
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.
4 secondary outcomes
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
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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dexanabinol, Sorafenib and Nab-paclitaxel in people with Hepatocellular Carcinoma and Pancreatic Cancer, run by e-Therapeutics PLC at 13 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, Spain, United Kingdom, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of dexanabinol given in combination with standard chemotherapies (time frame: For 29 days from the day of first dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2016.