A Study of Sativex® for Pain Relief in Patients With Advanced Malignancy.

Phase 2

Completed

Conditions: Palliative Care
Pain
Cancer

Interventions: Drug: Sativex Medium Dose
Drug: Sativex Low Dose
Drug: Sativex High Dose

Registration Number: NCT00530764

Lead Sponsor: GW Pharmaceuticals Ltd

Brief Summary: The purpose of this study is to determine the effective dose range and to demonstrate a non-effective dose range of Sativex in patients with advanced cancer, who experience inadequate pain relief even though they are on optimized chronic opioid therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 360

Inclusion Criteria

The patient has advanced active cancer for which there is no known curative therapy.
The patient is able (in the investigators opinion) and willing to comply with all study requirements.
The patient has a clinical diagnosis of cancer related pain, which is not wholly alleviated with their current opioid treatment.
The patient is receiving a sustained release (SR) fixed dose of opioid therapy (excluding Methadone). N.B. The opiate therapy must be Step III according to the World Health Organization (WHO) analgesic ladder.
The patient is willing to continue to take their regular daily baseline opioid regimen (SR) at the same dose, throughout the duration of study.

Exclusion Criteria

The patient should be excluded from entering study if they have received or are due to receive during the study period; chemotherapy, hormone therapy or radiotherapy, which, in the opinion of the investigator will affect their pain.
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.
Any known or suspected history of a diagnosed dependence disorder, current heavy alcohol consumption, current use of an illicit drug or current non prescribed use of any prescription drug.
The patient has poorly controlled epilepsy or recurrent seizures (i.e. at least one year since last seizure).
The patient has experienced myocardial infarction or clinically relevant cardiac 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 a clinically relevant arrhythmia or myocardial infarction.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sativex Medium Dose	Sativex Medium Dose	Range of 6 to 10 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 27mg THC and 25mg CBD.
Sativex Low Dose	Sativex Low Dose	Range of 1 to 4 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 10.8mg THC and 10mg CBD.
Sativex High Dose	Sativex High Dose	Range of 11 to 16 sprays per day. Each actuation of oromucosal spray delivers 2.7mg delta-9-tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD). Thus maximum daily dose is 43.2mg THC and 40mg CBD.

Primary Outcome Measures

Name	Time	Method
Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Average Pain Score From Baseline	5 Weeks: Baseline (first 3 days) - Week 5 (last 3 days)	A positive 30% pain response is defined as a reduction of at least 30% in the mean NRS average pain score from baseline to week 5 (last 3 days). The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. The average pain NRS was completed at the same time each day, i.e. bedtime in the evening.

Secondary Outcome Measures

Name	Time	Method
Change in Cumulative Average Pain Response Curves	Baseline to end of treatment (Week 5)	The cumulative response to treatment is the percentage changes from baseline in the mean NRS pain score as defined as the 30% response. The pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer.
Change in Mean Daily NRS Pain Score (Average Pain).	5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)	The average pain NRS was complete at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your pain or average pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. A negative value indicates an improvement in pain score from baseline.
Change in Mean Daily NRS Pain Score (Worst Pain).	5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)	The worst pain NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your worst pain in the last 24 hours" where 0 = no pain and 10 = pain as bad as you can imagine. No pain relates to the time prior to the onset of pain due to cancer. A negative value indicates an improvement in worst pain score from baseline.
Change in Sleep Disruption NRS	5 Weeks: Baseline - End of Treatment (Last 3 days of Week 5)	The sleep disruption NRS was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate how your pain disrupted your sleep last night?" where 0 = did not disrupt sleep and 10 = completely disrupted (unable to sleep at all). A negative value indicates an improvement in sleep disruption score from baseline.
Change in Brief Pain Inventory - Short Form (BPI-SF)	Baseline (Visit 2) and End of Treatment (End of Week 5 or premature termination)	The BPI-SF is a 14-item questionnaire that asks patients to rate pain over the prior week and the degree to which it interferes with activities on a 0 to 10 scale, where 0=no pain and 10=pain as bad as you can imagine. Severity is measured as worst pain, least pain, average pain, and pain right now. The severity composite score was calculated as the arithmetic mean of the four severity items(range 0-10). the minimum value is zero and maximum is 10. A higher score represents a poor outcome.
Change in Patient Assessment of Constipation Quality of Life (PAC-QoL)	Baseline (Visit 2) and End of Treatment (Week 5 or premature termination)	The PAC-QoL questionnaire consists of 28 questions divided into the following areas: 4 questions on physical discomfort, 8 questions on psychosocial discomfort, 11 questions on worries/concerns and 5 questions on satisfaction. The PAC-QoL was completed at baseline and then at the end of treatment. An overall score (range 0-4) was calculated at each visit and the difference determined. A positive difference in score represents an improvement.
Change in Patient Global Impression of Change - PGIC	End of Week 5	A 7-point Likert-type scale was used, with the question: 'Please assess the status of your pain due to cancer since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their pain caused by cancer which was used at Week 5 to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Change in Montgomery Asberg Depression Rating Scale (MADRS)	Baseline and End of Treatment (Week 5 or premature termination)	The MADRS comprises of 10 questions that are completed by the patient to determine their depression level. The MADRS was completed at Visit 2 (Baseline) prior to receiving the study drug and at Visit 4 (Week 5 or premature termination). Each item is scored on a 0-6 scale , where 0=no sadness to 6=extreme and continuous gloom and despondency, and the MADRS score is the sum of the 10 item scores (range 0-60). The higher the score the more severe the depression.

Trial Locations

Locations (109): A & A Pain Institute of St. Louis
🇺🇸
St. Louis, Missouri, United States
Vancouver Health Research Center
🇨🇦
Victoria, British Columbia, Canada
Office of Donald H. Berdeaux MD
🇺🇸
Great Falls, Montana, United States
ARO, Krajská zdravotni, K.Z. a.s, Nemocnice
🇨🇿
Teplice, Czech Republic
NZOZ Hospicjum Milosierdzia Bozego
🇵🇱
Gliwice, Poland
AR klinika FN Plzen -Ambulance pro lécbu bolesti
🇨🇿
Plzen, Czech Republic
Yashoda Hospital
🇮🇳
Andhra Pradesh, India
CHL - Apollo Hospitals
🇮🇳
Madhya Pradesh, India
Hospital Aranda de la Parra
🇲🇽
Leon, Mexico
Spitalul Clinic Judetean Sibiu Oncologie
🇷🇴
Sibiu, Romania
Bangalore Institute of Oncology
🇮🇳
Bangalore,, India
Apollo Hospital
🇮🇳
Hyderabaad, India
Indo-American Cancer Institute and Research Center
🇮🇳
Hyderabaad, India
Szpital Uniwersytecki w Krakowie
🇵🇱
Krakow, Poland
Spitalul Municipal Onesti
🇷🇴
Onesti, Jud. Bacau, Romania
Loma Linda University
🇺🇸
Loma Linda, California, United States
Desert Oasis Cancer Center
🇺🇸
Casa Grande, Arizona, United States
Office of Dr. Ronald Yanagihara
🇺🇸
Gilroy, California, United States
Clinical Pharmacology Services
🇺🇸
Tampa, Florida, United States
The Center for Clinical Research - Washington County Hospital
🇺🇸
Hagerstown, Maryland, United States
Fakultní nemocnice Na Bulovce
🇨🇿
Praha 8 - Liben, Czech Republic
UZ Leuven - Algologisch Centrum Anesthesiologie
🇧🇪
Pellenberg, Belgium
Schmerz- und Palliativzentrum Göppingen
🇩🇪
Göppingen, Germany
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Capital Comprehensive Cancer Care Clinic
🇺🇸
Jefferson City, Missouri, United States
Centre hospitalier Lyon Sud
🇫🇷
Pierre-Benite, France
Pacific Coast Hematology/Oncology Medical Group, Inc.
🇺🇸
Fountain Valley, California, United States
Lone Star Oncology
🇺🇸
Austin, Texas, United States
FN a LF UP Olomouc - Ambulance pro lécbu bolesti
🇨🇿
Olomouc, Czech Republic
CHU Charleroi (Hôpital civil de Charleroi)
🇧🇪
Charleroi, Belgium
Louisiana Research Associates
🇺🇸
New Orleans, Louisiana, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Huntsman Cancer Institute
🇺🇸
Salt Lake City, Utah, United States
Trialtech Research - Embassy Drive Medical Centre
🇿🇦
Hatfield, Pretoria, South Africa
Cancer Care Center of Tuscaloosa
🇺🇸
Tuscaloosa, Alabama, United States
RWTH Aachen Universität
🇩🇪
Aachen, Germany
Center of Hope for Cancer and Blood Disorders
🇺🇸
Riverdale, Georgia, United States
Fairfield General Hospital
🇬🇧
Bury, Lancashire, United Kingdom
Docrates Clinic
🇫🇮
Helsinki, Finland
Florida Institute of Medical Research
🇺🇸
Jacksonville, Florida, United States
St.-Marien-Hospital Lunen
🇩🇪
Lunen, Germany
Jawaharlal Nehru Cancer Hospital
🇮🇳
Madhya Pradesh, India
HU Puerta del Mar, Oncologia
🇪🇸
Cadiz, Spain
Hospital Virgen del Mar
🇪🇸
Almeria, Spain
Dr. Pirjol & Szpak Inc.
🇿🇦
Amanzimtoti, South Africa
Schmeiz - u Pallielivzendium Wiesbaden
🇩🇪
Wiesbaden, Germany
Htal Ángeles de Pedregal
🇲🇽
Mexico DF, Mexico
Basingstoke & North Hampshire NHS Foundation Trust
🇬🇧
Basingstoke, United Kingdom
West Suffolk Hospital
🇬🇧
Bury St Edmunds, United Kingdom
Eastleigh Breast Cancer Center
🇿🇦
Lynnwood, South Africa
Hospital Universitario de Bellvitge
🇪🇸
Feixa, Llarga, sn, Spain
Pretoria Urology Research Unit
🇿🇦
Hatfield, Pretoria, South Africa
Poradnia Leczenia Bolu
🇵🇱
Edyty Jakubow, Poland
Spitalul Judetean de Urgenta "Constantin Opris"
🇷🇴
Baia Mare, Maramures, Romania
Policnica Orizont-Oncologie Medicala
🇷🇴
Craiova, Romania
Spitalul Municipal Ploiesti
🇷🇴
Ploiesti, Romania
International Observatory on End of Life Care
🇬🇧
Lancaster, United Kingdom
St Bartholomew's Hospital
🇬🇧
London, United Kingdom
James Paget Hospital
🇬🇧
Gorleston on Sea, Norfolk, United Kingdom
Weston Area Health Trust
🇬🇧
Weston super Mare, United Kingdom
Edinburgh Cancer Research Centre (CRUK)
🇬🇧
Edinburgh, United Kingdom
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Clinic i Provincial
🇪🇸
Barcelona, Spain
Hospital Univ. Virgen de las Nieves
🇪🇸
Granada, Spain
New Cross Hospital
🇬🇧
Wolverhampton, United Kingdom
Regina Elana Cancer Institute
🇮🇹
Rom, Italy
Dir. S.C.D.U. Psicologia Clinica ed Oncologica
🇮🇹
Turin, Italy
Praticien hospitalier
🇫🇷
Tarbes, France
Marie Curie Hospice Holme Tower
🇬🇧
Penarth, United Kingdom
Gabrail Cancer Center
🇺🇸
Canton, Ohio, United States
Beth Israel Medical Center
🇺🇸
New York, New York, United States
Metropolitan Hospital Center
🇺🇸
New York, New York, United States
Summit Medical Group
🇺🇸
Berkeley Heights, New Jersey, United States
Center for Clinical Research
🇺🇸
Winston-Salem, North Carolina, United States
Four Seasons Hospice & Pallative Care
🇺🇸
Flat Rock, North Carolina, United States
Jules Bordet Institute
🇧🇪
Bruxelles, Belgium
Ambulance pro lécbu bolesti
🇨🇿
Ceské Budejovice, Czech Republic
Instituto Radio-oncológico Santiago (INRAD)
🇨🇱
Santiago, Chile
Ambulance pro lécbu bolesti, ARO
🇨🇿
Benešov, Czech Republic
Nemocnice Ceské Budejovice
🇨🇿
Ceské Budejovice, Czech Republic
Clínica Ciudad del Mar
🇨🇱
Viña del Mar, Chile
FN Hradec Králové - Klinika onkologie a radioterapie
🇨🇿
Hradec Králové, Czech Republic
Nemocnice Jihlava
🇨🇿
Jihlava, Czech Republic
Deenanath Mangeshkar Hospital and Research Center
🇮🇳
Pune, India
Meenakshi Mission Hospital & Research Centre
🇮🇳
Madurai, India
Pain Clinic
🇿🇦
Cape Town, South Africa
Medi Clinic
🇿🇦
Bloemfontein, South Africa
Oncology/Haematology Dept Research Unit
🇿🇦
Kimberley, South Africa
Hospital de la Rioja
🇪🇸
Logrono, Spain
Hospital Los Montalvos
🇪🇸
Salamanca, Spain
The Royal Marsden NHS Foundation Trust
🇬🇧
Sutton, United Kingdom
Spitalul Judetean de Urgenta "Sf. Ioan cel Nou"
🇷🇴
Suceava, Romania
CBCC- Apollo Hospital
🇮🇳
Gandhinagar, India
Bhagwaan Mahaveer Cancer Hospital and Research Centre
🇮🇳
Jaipur, India
All India Institute of Medical Sciences
🇮🇳
New Delhi, India
Jehangir Clinical Development Centre Pvt. Ltd.
🇮🇳
Pune, India
Seroc Cancer Center
🇮🇳
Rajasthan, India
Beskidzkie Centrum Onkologii im. Jana Pawla
🇵🇱
Bielsko-Biala, Poland
Wojewodzki Szpital Specjalistyczny im. M. Kopernika
🇵🇱
Gdansk, Poland
Wielkopolskie Centrum Onkologii
🇵🇱
Poznan, Poland
Niepubliczny Zaklad Opieki Zdrowotnej
🇵🇱
Tychy, Poland
Centrum Onkologii - Instytut im. M. Sklodowskiej - Curie
🇵🇱
Warszawa, Poland
Spitalul Judetean de Urgenta Braila
🇷🇴
Braila, Jud. Braila, Romania
Hospice "Casa Sperantei"
🇷🇴
Brasov, Romania
Spitalul Universitar de Urgenta Elias
🇷🇴
Bucuresti, Romania
S.C. IanuliMed S.R.L. Oncologie Medicala
🇷🇴
Bucuresti, Romania
District Hospital Dr. Alexandru Simionescu
🇷🇴
Hunedoara, Romania
Centrul de Oncologie Medicala
🇷🇴
Iasi, Romania
University of California San Diego
🇺🇸
La Jolla, California, United States