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

Pain Clinical Trial

— SPRAY  

Official title:

A Double Blind, Randomized, Placebo Controlled, Parallel Group Dose-range Exploration Study of Sativex® in Relieving Pain in Patients With Advanced Cancer, Who Experience Inadequate Analgesia During Optimized Chronic Opioid Therapy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00530764
• Other study ID #: GWCA0701
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2007
• Last updated: June 13, 2013
• Start date: November 2007
• Est. completion date: January 2010

Study information

• Verified date: June 2013
• Source: GW Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cancer
• Pain
• Palliative Care

Intervention

Drug:
• 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 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 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
GW Pharmaceuticals Ltd.	Quintiles, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Chile,  Czech Republic,  Finland,  France,  Germany,  India,  Italy,  Mexico,  Poland,  Romania,  South Africa,  Spain,  United Kingdom, 

References & Publications (1)

Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, McQuade R, Wright S, Fallon MT. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With at Least 30% Improvement in Numerical Rating Scale (NRS) Average Pain Score From Baseline	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.	5 Weeks: Baseline (first 3 days) - Week 5 (last 3 days)	No
Secondary	Change in Cumulative Average Pain Response Curves	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.	Baseline to end of treatment (Week 5)	No
Secondary	Change in Mean Daily NRS Pain Score (Average Pain).	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.	5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)	No
Secondary	Change in Mean Daily NRS Pain Score (Worst Pain).	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.	5 Weeks: Baseline (first 3 days) - End of Treatment (last 3 days of week 5)	No
Secondary	Change in Sleep Disruption NRS	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.	5 Weeks: Baseline - End of Treatment (Last 3 days of Week 5)	No
Secondary	Change in Brief Pain Inventory - Short Form (BPI-SF)	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.	Baseline (Visit 2) and End of Treatment (End of Week 5 or premature termination)	No
Secondary	Change in Patient Assessment of Constipation Quality of Life (PAC-QoL)	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.	Baseline (Visit 2) and End of Treatment (Week 5 or premature termination)	No
Secondary	Change in Patient Global Impression of Change - PGIC	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.	End of Week 5	No
Secondary	Change in Montgomery Asberg Depression Rating Scale (MADRS)	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.	Baseline and End of Treatment (Week 5 or premature termination)	Yes