Clinical trial NCT01809106: 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.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cancer
Cancer Pain
Keywords: cancer pain
major opioid
analgesics
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2013-03-12
Enrollment: 518
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Non-Responder (NR) Participants
timeFrame: 28 days
Secondary outcomes:
measure: Proportion of Full-responder
timeFrame: 28 days
Other outcomes:
measure: The Opioid Escalation Index
timeFrame: 28 days
Locations:
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova Azienda Ospedaliera
state: RE
city: Catania
country: Italy
facility: Ospedale S. Marta
city: Milano
country: Italy
facility: Fondazione IRCCS - Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Istituto Scientifico San Raffaele
city: Morbegno
country: Italy
facility: Azienda Ospedaliera Valtellina-Valchiavenna
city: Piacenza
country: Italy
facility: Ospedale Civile di Piacenza
city: Sesto San Giovanni
country: Italy
facility: Multimedica
city: Torino
country: Italy
facility: Ospedale San Giovanni Battista di Torino
city: Torino
country: Italy
facility: Ospedale Gradenigo
Study officials:
affiliation: Mario Negri Institute of Pharmacological Research - IRCCS
name: Oscar Corli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1186/1477-7525-4-7.
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.
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.
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.
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.
citation: Corli O, Roberto A, Bennett MI, Galli F, Corsi N, Rulli E, Antonione R. Nonresponsiveness and Susceptibility of Opioid Side Effects Related to Cancer Patients' Clinical Characteristics: A Post-Hoc Analysis. Pain Pract. 2018 Jul;18(6):748-757. doi: 10.1111/papr.12669. Epub 2018 Jan 17.
citation: Corli O, Floriani I, Roberto A, Montanari M, Galli F, Greco MT, Caraceni A, Kaasa S, Dragani TA, Azzarello G, Luzzani M, Cavanna L, Bandieri E, Gamucci T, Lipari G, Di Gregorio R, Valenti D, Reale C, Pavesi L, Iorno V, Crispino C, Pacchioni M, Apolone G; CERP STUDY OF PAIN GROUP (List of collaborators). Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids. Ann Oncol. 2016 Jun;27(6):1107-1115. doi: 10.1093/annonc/mdw097. Epub 2016 Mar 2.