A Safety Study of Sativex in Combination With Dose-intense Temozolomide in Patients With Recurrent Glioblastoma

NCT01812603 | Completed Phase 1

• 1 other identifier: GWCA1208 Part A
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 5

Brief Summary

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 A will be reported here.

Conditions

Cancer

Keywords

Cancer; Safety

Outcome Measures

Primary Outcomes (1)

• The incidence of adverse events in patients receiving Sativex in combination with dose-intense Temozolomide in the open-label phase of the study

  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.

  Study Day 1 - Day 358

Secondary Outcomes (2)

• The number of patients with Progression Free Survival at six months (PFS6)

  Study Day 1 - Day 190

• Overall Survival

  Study Day 1 - Day 358

Study Arms (1)

Sativex and Dose-Intense Temozolomide

EXPERIMENTAL

Patients will received Sativex and Dose-Intense Temozolomide and in open-label manner

Drug: Sativex

Interventions

Sativex DRUG

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).

Also known as: THC/CBD spray, Nabiximols, GW-1000-02

Sativex and Dose-Intense Temozolomide

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (5)

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JY, United Kingdom

Location

St James's Institute of Oncology, St James's University Hospital

Leeds, Yorkshire, LS9 7TF, United Kingdom

Location

Bristol Haematology & Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Guy's and St Thomas NHS Foundation Trust, of St Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Twelves C, Sabel M, Checketts D, Miller S, Tayo B, Jove M, Brazil L, Short SC; GWCA1208 study group. A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma. Br J Cancer. 2021 Apr;124(8):1379-1387. doi: 10.1038/s41416-021-01259-3. Epub 2021 Feb 24.

  PMID: 33623076 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

nabiximols

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 18, 2013
• Study Start: September 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: June 1, 2016
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

GB (5)