A Safety Study of Sativex Compared With Placebo (Both With Dose-intense Temozolomide) in Recurrent Glioblastoma Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by GW Research Ltd
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd
ClinicalTrials.gov Identifier:
NCT01812616
First received: March 14, 2013
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

An open-label phase to assess the frequency and severity of adverse events in recurrent glioblastoma patients receiving Sativex in combination with dose-intense Temozolomide (Part A). A randomisation phase to assess the safety of Sativex compared with placebo (Part B). Part B will be reported here.


Condition Intervention Phase
Cancer
Drug: Sativex
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Two Part Study to Assess the Tolerability, Safety and Pharmacodynamics of Sativex in Combination With Dose-intense Temozolomide in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by GW Research Ltd:

Primary Outcome Measures:
  • Incidence of Adverse Events as a Measure of Patient Safety. [ Time Frame: Study Day 1 - Day 358 ] [ Designated as safety issue: Yes ]
    Adverse events will be coded according to the current medical dictionary for regular activities graded using the Common Terminology Criteria for Adverse Events criteria. The number of patients who experienced an adverse event whilst on treatment will be presented.


Secondary Outcome Measures:
  • The number of patients with Progression Free Survival at six months (PFS6) [ Time Frame: Study Day 1 - Day 190 ] [ Designated as safety issue: Yes ]
    PFS6 will be assessment at Visit 11 (Day 190). Progression of disease will be determined from Response Assessment in Neuro-Oncology tumour assessment (based on Magnetic Resonance Imaging scans). The number of patients with PFS6 will be presented for the individual treatment groups.

  • Overall Survival [ Time Frame: Study Day 1 - Day 358 ] [ Designated as safety issue: Yes ]
    Overall survival will be assessed at the end of the treatment visit (Day 358 or at early termination). The number of surviving patients in each group from the randomisation phase (Part B) will be presented.


Estimated Enrollment: 20
Study Start Date: September 2014
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sativex and Dose-Intense Temozolomide
Patients will received Sativex and Dose-Intense Temozolomide in a double-blind manner
Drug: Sativex
Administered orally as a spray to the cheek according to a standard dose titration regimen, until patients reach a maximum tolerated dose (maximum 12 sprays per day). Each spray delivers 100 μl (Δ9tetrahydrocannabinol (THC), 27 mg/ml: Cannabidiol (CBD), 25 mg/ml).
Other Names:
  • THC/CBD spray
  • Nabiximols
  • GW-1000-02
Placebo Comparator: Placebo and Dose-Intense Temozolomide
Patients will received placebo and Dose-Intense Temozolomide and in double-blind manner
Drug: Placebo
Administered orally as a spray to the cheek according to a standard dose titration regimen, until patients reach a maximum tolerated dose (maximum 12 sprays per day). Each spray delivers 100 μl ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and Food, Drugs & Cosmetics (FD&C)certified color additives; FD&C Yellow No.5 (E102 tartrazine) (0.0260%), FD&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%).
Other Name: Placebo comparator

Detailed Description:

Patients will receive Sativex and dose-intense Temozolomide in an open-label phase. The incidence of adverse events will be monitored (Part A). An investigator led Safety Review Team will assess the safety profile of the open-label patients and decide whether the study can progress to the randomisation phase (Part B). Patients who enrol in the randomisation phase patients will receive either Sativex or placebo. The safety of Sativex compared to placebo will be assessed by pharmacokinetic analysis of Temozolomide and its metabolites, clinical laboratory tests, adverse events and vital signs.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient is willing and able to give informed consent for participation in the study.
  • Patient is aged 18 years or above.
  • Histopathologically confirmed diagnosis of grade four Glioblastoma Multiforme as per World Health Organisation classification.
  • Evidence of patients first tumour progression (as determined by Revised Assessment in Neuro-Oncology) following radiation and first line chemotherapy with Temozolomide.
  • If taking steroids, then the dose must be stable or decreasing.
  • Karnofsky performance scale of 60% or greater.
  • Patient is able (in the investigators opinion) and willing to comply with all study requirements.
  • Patient is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries.
  • Patient is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

  • Patients with Glioblastoma Multiforme secondary to low-grade glioma or anaplastic glioma (anaplastic astrocytoma or anaplastic oligodendroglioma).
  • Patients currently receiving treatment for recurrent Glioblastoma Multiforme.
  • Less than a four week interval since prior chemotherapy.
  • Less than a 12 week interval since prior radiotherapy unless there is either: a) histopathology confirmation of recurrent tumour, or b) new enhancement on Magnetic Resonance Imaging outside of the radiotherapy treatment field.
  • Presence of extra-cranial metastatic disease.
  • Any surgery, including intracranial biopsy (not including minor diagnostic procedures such as lymph node biopsy) within two weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
  • Any history of a different malignancy unless the patient has remained disease-free for at least three years and are at low risk for recurrence of that malignancy (cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin are exempt from this criterion if treatment has occurred).
  • Have previously received first line chemotherapy other than Temozolomide.
  • Presents with Leptomeningeal dissemination.
  • Have previously received stereotactic radiotherapy, convection enhanced delivery or brachytherapy (as gliosis/scarring from these modalities may limit delivery).
  • The patient is currently using or has used cannabis or cannabinoid based medications within 30 days of study entry and is unwilling to abstain for the duration of the study.
  • Any known or suspected history of a substance abuse/dependence disorder, current heavy alcohol consumption (>60g of pure alcohol per day for men, >40 g of pure alcohol per day for women), current use of an illicit drug or current non prescribed use of any prescription drug.
  • Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
  • Has experienced myocardial infarction or clinically significant dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the patient at risk of clinically significant arrhythmia or myocardial infarction.
  • Has grade 3 or above toxicity by Common Terminology Criteria for Adverse Events criteria.
  • Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (however a male condom should not be used in conjunction with a female condom).
  • Female patients who are pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
  • Patient who have received an Investigational Medicinal Product within the four weeks prior to the screening visit.
  • Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the result of the study, or the patient's ability to participate in the study.
  • Travel outside the country of residence planned during the study.
  • Patients previously enrolled into this study and received either Investigational Medicinal Product or Dose-Intense Temozolomide.
  • Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product.
  • Any known allergy to or other intolerability to Temozolomide.
  • Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study.
  • Unwilling to abstain from donation of blood during the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01812616

Contacts
Contact: Richard Potts 00 44 1223 266800 rp@gwpharm.com

Locations
United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust Not yet recruiting
Bebington, Wirral, United Kingdom, CH63 4JY
Contact: Brian J Haylock, MBBS    +44 (0) 151 334 1155    brian.haylock@clatterbridgecc.nhs.uk   
Contact: Barbara King    +44 (0) 151 334 1155    Barbara.King@clatterbridgecc.nhs.uk   
Principal Investigator: Brian J Haylock, MBBS         
St James's Institute of Oncology, St James's University Hospital Not yet recruiting
Leeds, Yorkshire, United Kingdom, LS9 7TF
Contact: Christopher Twelves, MD    +44 (0) 113 20 68186    c.j.twelves@leeds.ac.uk   
Contact: Susan Short, MD    +44 (0) 113 343 8434    s.c.short@leeds.ac.uk   
Principal Investigator: Christopher J Twelves, MD         
Bristol Haematology & Oncology Centre Not yet recruiting
Bristol, United Kingdom, BS2 8ED
Contact: Kirsten Hopkins, MD    01173423008    kirsten.hopkins@UHBristol.nhs.uk   
Contact: Matt Baxter    01173426735    matt.baxter@uhbristol.nhs.uk   
Principal Investigator: Kirsten Hopkins, MD         
Guy's & St Thomas' NHS Foundation Trust, of St Thomas' Hospital Not yet recruiting
London, United Kingdom, SE1 7EH
Contact: Lucy Brazil, MD    020 7188 1476    lucy.brazil@gstt.nhs.uk   
Contact       BrainResearchTeam@gstt.nhs.uk   
Principal Investigator: Lucy Brazil, MD         
The Christie NHS Foundation Trust Not yet recruiting
Manchester, United Kingdom, M20 4BX
Contact: Catherine McBain, MD    +44 (0) 161 918 7008    catherine.mcbain@christie.nhs.uk   
Contact: Alex Stordy    01614468442    alex.stordy@christie.nhs.uk   
Principal Investigator: Catherine McBain, MD         
Sponsors and Collaborators
GW Research Ltd
Investigators
Study Chair: Susan Short, MD Leeds Institute of Cancer and Pathology, Wellcome Trust Brenner Buidling, St James Univeristy Hospital, Leeds
Principal Investigator: Christopher Twelves, MD St James's Institute of Oncology, St James's University Hospital, Leeds.
Principal Investigator: Lucy Brazil, MD St. Thomas' Hospital, Clinical Oncology, London.
Principal Investigator: Catherine McBain, MD Dpt. Clinical Oncology, The Christie, Manchester.
Principal Investigator: Brian Haylock, MD The Clatterbridge Cancer Centre, Bebington, Wirral
Principal Investigator: Kirsten Hopkins, MD Bristol Haematology & Oncology Centre
  More Information

No publications provided

Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT01812616     History of Changes
Other Study ID Numbers: GWCA1208 Part B
Study First Received: March 14, 2013
Last Updated: September 2, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GW Research Ltd:
Cancer
Safety

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014