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

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.

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.

Study Overview

• Status: Completed
• Conditions: Pain; Cancer; Palliative Care
• Intervention / Treatment: Drug: Sativex Low Dose; Drug: Sativex Medium Dose; Drug: Sativex High Dose

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1000
    • Jules Bordet Institute
  • Charleroi, Belgium, 6000
    • CHU Charleroi (Hôpital civil de Charleroi)
  • Pellenberg, Belgium, 3212
    • UZ Leuven - Algologisch Centrum Anesthesiologie
• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 1R2
      • Vancouver Health Research Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Chile
  • Santiago, Chile
    • Instituto Radio-oncológico Santiago (INRAD)
  • Viña del Mar, Chile
    • Clínica Ciudad del Mar
• Czech Republic
  • Benešov, Czech Republic, 25601
    • Ambulance pro lécbu bolesti, ARO
  • Ceské Budejovice, Czech Republic, 370 01
    • Ambulance pro lécbu bolesti
  • Ceské Budejovice, Czech Republic, 370 87
    • Nemocnice Ceske Budejovice
  • Hradec Králové, Czech Republic, 500 05
    • FN Hradec Králové - Klinika onkologie a radioterapie
  • Jihlava, Czech Republic, 58633
    • Nemocnice Jihlava
  • Olomouc, Czech Republic, 775 20
    • FN a LF UP Olomouc - Ambulance pro lécbu bolesti
  • Plzen, Czech Republic, 304 60
    • AR klinika FN Plzen -Ambulance pro lécbu bolesti
  • Praha 8 - Liben, Czech Republic, 180 81
    • Fakultni nemocnice Na Bulovce
  • Teplice, Czech Republic, 41501
    • ARO, Krajská zdravotni, K.Z. a.s, Nemocnice
• Finland
  • Helsinki, Finland, 00150
    • Docrates Clinic
• France
  • Pierre-Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Tarbes, France, 65000
    • Praticien hospitalier
• Germany
  • Aachen, Germany, 52074
    • RWTH Aachen Universität
  • Göppingen, Germany, 73033
    • Schmerz- und Palliativzentrum Göppingen
  • Lunen, Germany, 44534
    • St.-Marien-Hospital Lünen
  • Wiesbaden, Germany, 65189
    • Schmeiz - u Pallielivzendium Wiesbaden
• India
  • Andhra Pradesh, India, 500 082
    • Yashoda Hospital
  • Bangalore,, India, 560027
    • Bangalore Institute of Oncology
  • Gandhinagar, India
    • CBCC- Apollo Hospital
  • Hyderabaad, India, 500033
    • Apollo Hospital
  • Hyderabaad, India, 500034
    • Indo-American Cancer Institute and Research Center
  • Jaipur, India, 302017
    • Bhagwaan Mahaveer Cancer Hospital and Research Centre
  • Madhya Pradesh, India, 452 008
    • CHL - Apollo Hospitals
  • Madhya Pradesh, India, 462 001
    • Jawaharlal Nehru Cancer Hospital
  • Madurai, India, 625107
    • Meenakshi Mission Hospital & Research Centre
  • New Delhi, India, 110 029
    • All India Institute of medical Sciences
  • Pune, India, 411001
    • Jehangir Clinical Development Centre Pvt. Ltd.
  • Pune, India
    • Deenanath Mangeshkar Hospital and Research Center
  • Rajasthan, India, 302 013
    • Seroc Cancer Center
• Italy
  • Rom, Italy, 00144
    • Regina Elana Cancer Institute
  • Turin, Italy, 10128
    • Dir. S.C.D.U. Psicologia Clinica ed Oncologica
• Mexico
  • Leon, Mexico, 37000
    • Hospital Aranda de la Parra
  • Mexico DF, Mexico, 10700
    • Htal Ángeles de Pedregal
• Poland
  • Bielsko-Biala, Poland, 43-300
    • Beskidzkie Centrum Onkologii im. Jana Pawla
  • Edyty Jakubow, Poland
    • Poradnia Leczenia Bolu
  • Gdansk, Poland, 80-803
    • Wojewodzki Szpital Specjalistyczny im. M. Kopernika
  • Gliwice, Poland, 44-101
    • NZOZ Hospicjum Milosierdzia Bozego
  • Krakow, Poland, 31-631
    • Szpital Uniwersytecki W Krakowie
  • Poznan, Poland, 61-866
    • Wielkopolskie Centrum Onkologii
  • Tychy, Poland, 43-100
    • Niepubliczny Zaklad Opieki Zdrowotnej
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Instytut im. M. Sklodowskiej - Curie
• Romania
  • Baia Mare, Maramures, Romania, 430031
    • Spitalul Judetean de Urgenta "Constantin Opris"
  • Braila, Jud. Braila, Romania, 810325
    • Spitalul Județean de Urgență Brăila
  • Brasov, Romania, 500074
    • Hospice "Casa Sperantei"
  • Bucuresti, Romania, 011461
    • Spitalul Universitar de Urgenta Elias
  • Bucuresti, Romania, 020962
    • S.C. IanuliMed S.R.L. Oncologie Medicala
  • Craiova, Romania, 200535
    • Policnica Orizont-Oncologie Medicala
  • Hunedoara, Romania, 331057
    • District Hospital Dr. Alexandru Simionescu
  • Iasi, Romania, 700106
    • Centrul de Oncologie Medicala
  • Onesti, Jud. Bacau, Romania, 601048
    • Spitalul Municipal Onesti
  • Ploiesti, Romania, 100337
    • Spitalul Municipal Ploiesti
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean Sibiu Oncologie
  • Suceava, Romania, 720237
    • Spitalul Judetean de Urgenta "Sf. Ioan cel Nou"
• South Africa
  • Amanzimtoti, South Africa, 4126
    • Dr. Pirjol & Szpak Inc.
  • Bloemfontein, South Africa, 9301
    • Medi Clinic
  • Cape Town, South Africa, 8001
    • Pain Clinic
  • Hatfield, Pretoria, South Africa, 0083
    • Pretoria Urology Research Unit
  • Hatfield, Pretoria, South Africa, 0083
    • Trialtech Research - Embassy Drive Medical Centre
  • Kimberley, South Africa, 8301
    • Oncology/Haematology Dept Research Unit
  • Lynnwood, South Africa, 0041
    • Eastleigh Breast Cancer Center
• Spain
  • Almeria, Spain, 04003
    • Hospital Virgen del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Cadiz, Spain, 11009
    • HU Puerta del Mar, Oncologia
  • Feixa, Llarga, sn, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Granada, Spain, 180114
    • Hospital Univ. Virgen de las Nieves
  • Logrono, Spain, 26001
    • Hospital de la Rioja
  • Salamanca, Spain, 37192
    • Hospital Los Montalvos
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9NA
    • Basingstoke & North Hampshire NHS Foundation Trust
  • Bury St Edmunds, United Kingdom, IP33 2QZ
    • West Suffolk Hospital
  • Bury, Lancashire, United Kingdom, BL9 7TD
    • Fairfield General Hospital
  • Edinburgh, United Kingdom, EH4 2XR
    • Edinburgh Cancer Research Centre (CRUK)
  • Gorleston on Sea, Norfolk, United Kingdom, NR31 6LA
    • James Paget Hospital
  • Lancaster, United Kingdom, LA1 4YT
    • International Observatory on End of Life Care
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital
  • London, United Kingdom, SW3 6LL
    • The Royal Marsden NHS Foundation Trust
  • Penarth, United Kingdom, CF64 3YR
    • Marie Curie Hospice Holme Tower
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
  • Weston super Mare, United Kingdom, BS23 4TQ
    • Weston Area Health Trust
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35406
      • Cancer Care Center of Tuscaloosa
  • Arizona
    • Casa Grande, Arizona, United States, 85222
      • Desert Oasis Cancer Center
  • California
    • Fountain Valley, California, United States, 92708
      • Pacific Coast Hematology/Oncology Medical Group, Inc.
    • Gilroy, California, United States, 95020
      • Office of Dr. Ronald Yanagihara
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • Loma Linda, California, United States, 92354
      • Loma Linda University
  • Florida
    • Jacksonville, Florida, United States, 32257
      • Florida Institute of Medical Research
    • Tampa, Florida, United States, 33617
      • Clinical Pharmacology Services
  • Georgia
    • Riverdale, Georgia, United States, 30274
      • Center of Hope for Cancer and Blood Disorders
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • The Center for Clinical Research - Washington County Hospital
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Capital Comprehensive Cancer Care Clinic
    • St. Louis, Missouri, United States, 63141
      • A & A Pain Institute of St. Louis
  • Montana
    • Great Falls, Montana, United States, 59405
      • Office of Donald H. Berdeaux MD
  • New Jersey
    • Berkeley Heights, New Jersey, United States, 07922
      • Summit Medical Group
  • New York
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10029
      • Metropolitan Hospital Center
  • North Carolina
    • Flat Rock, North Carolina, United States, 28731
      • Four Seasons Hospice & Pallative Care
    • Winston-Salem, North Carolina, United States, 27103
      • Center for Clinical Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Austin, Texas, United States, 78759
      • Lone Star Oncology
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: GW-1000-02
Experimental: 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.	Drug: 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.; Other Names: GW-1000-02
Experimental: 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.	Drug: 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.; Other Names: GW-1000-02
No Intervention: Placebo; Range of 1-16 sprays per day of placebo spray.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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
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)

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Quintiles, Inc.

Publications and helpful links

General Publications

• 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. 2012 May;13(5):438-49. doi: 10.1016/j.jpain.2012.01.003. Epub 2012 Apr 5.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: September 13, 2007
• First Submitted That Met QC Criteria: September 13, 2007
• First Posted (Estimate): September 17, 2007

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 13, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Cancer; Pain; Palliative
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Anticonvulsants; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol; Cannabidiol; Nabiximols
• Other Study ID Numbers: GWCA0701