RCT Comparing the Analgesic Efficacy of 4 Therapeutic Strategies Based on 4 Different Major Opioids (Fentanyl, Oxycodone, Buprenorphine vs Morphine) in Cancer Patients With Moderate/Severe Pain, at the Moment of Starting 3rd Step of WHO Analgesic Ladder.

Cancer Clinical Trial

— CERP  

Official title:

RCT Comparing the Analgesic Efficacy of 4 Therapeutic Strategies Based on 4 Different Major Opioids (Fentanyl, Oxycodone, Buprenorphine vs Morphine) in Cancer Patients With Moderate/Severe Pain, at the Moment of Starting 3rd Step of WHO Analgesic Ladder.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01809106
• Other study ID #: Studio CERP
• Status: Completed
• Phase: Phase 4
• First received: March 8, 2013
• Last updated: November 20, 2015
• Start date: April 2011
• Est. completion date: October 2014

Study information

• Verified date: October 2015
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines AgencyItaly: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Pain, in neoplastic disease, is a symptom with severe negative impact on the quality of life of patients and a high incidence, with values around 70-90% in advanced and metastatic stages. Than 20 years the main reference for the pharmacological treatment of cancer pain are the guidelines produced by the World Health Organization (WHO). This document shows that the use of opioid drugs is the mainstay of treatment, with particular reference to opioids "major" (3 rd step of the analgesic ladder). The 4 opioids more most commonly prescribed in Italy (oral morphine and oxycodone, fentanyl and buprenorphine transdermal), based on the data currently available, have an analgesic effect would partly overlap but with different percentages of non-responders (NR), a different need to increase the dose over time to maintain adequate analgesia, a different action to the switch to another molecule for ineffectiveness analgesic. The observations described suggest that opioids, although they belong to the same family drug may not be fully comparable with regard to the clinical effects products. Important differences are known on the pharmacokinetic and pharmacodynamic and, more recently, also in terms of pharmacogenomics. This is a comparative study of analgesic strategies based on the use of the 4 mentioned opioids, going to look for possible differences in terms of analgesic efficacy, changes in dose over time, use of switch or permanent abandonment of treatment, parallel to the contour of the side effects. The associated sub-project will link the structure gene of patients and clinical results have emerged.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 518
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients with diagnostic (histological or cytological) evidence of locally advanced or metastatic solid tumour;

• with average pain intensity = 4, measured with NRS and related to the last 24 hours, due to the cancer, requiring for the first time an analgesic treatment with 3rd step/WHO opioids

• with life expectancy > one month

• "strong" opioid naïve;

• eligible to take any of the medications under evaluation, by TDS or by mouth;

• with age = 18 years;

Exclusion Criteria:

• Patients recruited in other researches that conflict or may confound the conduction and results of the present study;

• Lack of informed consent;

• with presence of other diseases, including psychiatric/mental illness, severe senile or other form of dementia, that can interfere with participation and compliance with the study protocol or can contraindicate the use of the investigational drugs;

• with presence of co-morbidities, which could create potentially dangerous drug interactions with opioids (eg, use of macrolide antibiotics or antifungal,….);

• any kind of contraindications to the use of opioid drugs;

• Patients with a known story, past or current, of drugs abuse or addiction;

• Use of drugs which presents a combination of opioids and other molecule (as NSAIDs, paracetamol, naloxone, ..);

• Patients who cannot guarantee regular follow-up visits for logistic or geographic reasons;

• Need of starting 3rd step treatment in an "emergency clinical situation" that do not allow the correct procedures of randomization;

• diagnosis of primary brain tumor or leukaemia;

• diagnosis of chronic renal failure;

• patients with antalgic radiotherapy or radio-metabolic therapy in progress or completed less than 14 days before study;

• patients starting a first line chemotherapy simultaneously to the beginning of the study;

• other types of analgesic treatments, including local-regional anesthetic techniques or neurosurgical /ablative methods.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Cancer Pain

Intervention

Drug:
• Morphine
60 mg /24 ore
• Fentanyl
25 microg/h
• Buprenorphine
35 microg/h
• Oxycodone
40 mg /24 ore

Locations

Country	Name	City	State
Italy	Ospedale S. Marta	Catania
Italy	Fondazione IRCCS - Istituto Nazionale dei Tumori	Milano
Italy	Istituto Scientifico San Raffaele	Milano
Italy	Azienda Ospedaliera Valtellina-Valchiavenna	Morbegno
Italy	Ospedale Civile di Piacenza	Piacenza
Italy	Arcispedale S. Maria Nuova Azienda Ospedaliera	Reggio Emilia	RE
Italy	Multimedica	Sesto San Giovanni
Italy	Ospedale Gradenigo	Torino
Italy	Ospedale San Giovanni Battista di Torino	Torino

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Apolone G, Bertetto O, Caraceni A, Corli O, De Conno F, Labianca R, Maltoni M, Nicora M, Torri V, Zucco F; Cancer Pain Outcome Research Study Group. Pain in cancer. An outcome research project to evaluate the epidemiology, the quality and the effects of pain treatment in cancer patients. Health Qual Life Outcomes. 2006 Feb 2;4:7. — View Citation

Apolone G, Corli O, Caraceni A, Negri E, Deandrea S, Montanari M, Greco MT; Cancer Pain Outcome Research Study Group (CPOR SG) Investigators. Pattern and quality of care of cancer pain management. Results from the Cancer Pain Outcome Research Study Group. Br J Cancer. 2009 May 19;100(10):1566-74. doi: 10.1038/sj.bjc.6605053. Epub 2009 Apr 28. — View Citation

Apolone G, Deandrea S, Montanari M, Corli O, Greco MT, Cavuto S. Evaluation of the comparative analgesic effectiveness of transdermal and oral opioids in cancer patients: a propensity score analysis. Eur J Pain. 2012 Feb;16(2):229-38. doi: 10.1002/j.1532-2149.2011.00020.x. Epub 2011 Dec 19. — View Citation

Corli O, Montanari M, Deandrea S, Greco MT, Villani W, Apolone G. An exploratory analysis on the effectiveness of four strong opioids in patients with cancer pain. Pain Med. 2012 Jul;13(7):897-907. doi: 10.1111/j.1526-4637.2012.01408.x. Epub 2012 Jun 8. — View Citation

Greco MT, Corli O, Montanari M, Deandrea S, Zagonel V, Apolone G; Writing Protocol Committee; Cancer Pain Outcome Research Study Group (CPOR SG) Investigators. Epidemiology and pattern of care of breakthrough cancer pain in a longitudinal sample of cancer patients: results from the Cancer Pain Outcome Research Study Group. Clin J Pain. 2011 Jan;27(1):9-18. doi: 10.1097/AJP.0b013e3181edc250. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Opioid Escalation Index	The proportion of subjects with an increase of opioid daily dose > 5% compared with the basal dosage (OEI%).	28 days	No
Primary	Proportion of Non-Responder (NR) Participants	Evaluation of the proportion of Non-Responder (NR) participants. NR correspond to the subjects who do not report any analgesic effects, with a P.I.D. (pain intensity difference) from visit 6 and visit 1 =/< 0%, (using a 0-10 NRS ). It includes the situations of average pain intensity "stable" or "worsened" at day 28 compared with baseline values.	28 days	No
Secondary	Proportion of Full-responder	Evaluation of the proportion of subjects who report full analgesia (full responders: FR). FR is operationally defined as a patient with a P.I.D. =/> 30% from visit 6 and visit 1 (NRS 0 to 10).	28 days	No

External Links

•   Info of the study