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.

NCT01809106 | Completed Phase 4 Results

• 1 other identifier: Studio CERP
• Study Type: interventional
• Target: 518
• Locations: 1 country
• Sites: 9

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.

Conditions

Cancer; Cancer Pain

Keywords

cancer pain; major opioid; analgesics

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Proportion of Full-responder

  28 days

Other Outcomes (1)

• The Opioid Escalation Index

  28 days

Study Arms (4)

Morphine

ACTIVE COMPARATOR

Drug: Morphine

Oxycodone

EXPERIMENTAL

Drug: Oxycodone

Buprenorphine

EXPERIMENTAL

Drug: Buprenorphine

Fentanyl

EXPERIMENTAL

Drug: Fentanyl

Interventions

Morphine DRUG

60 mg /24 ore

Morphine

Fentanyl DRUG

25 microg/h

Fentanyl

Buprenorphine DRUG

35 microg/h

Buprenorphine

Oxycodone DRUG

40 mg /24 ore

Oxycodone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (9)

Ospedale S. Marta

Catania, Italy, Italy

Location

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, Italy, Italy

Location

Istituto Scientifico San Raffaele

Milan, Italy, Italy

Location

Azienda Ospedaliera Valtellina-Valchiavenna

Morbegno, Italy, Italy

Location

Multimedica

Sesto San Giovanni, Italy, Italy

Location

Ospedale Gradenigo

Torino, Italy, Italy

Location

Ospedale Civile di Piacenza

Piacenza, Piacenza, 29100, Italy

Location

Arcispedale S. Maria Nuova Azienda Ospedaliera

Reggio Emilia, RE, 42100, Italy

Location

Ospedale San Giovanni Battista di Torino

Torino, Torino, 10126, Italy

Location

Related Publications (7)

• 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.

  PMID: 16457716 BACKGROUND

• 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.

  PMID: 19401688 BACKGROUND

• 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.

  PMID: 20842024 BACKGROUND

• 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.

  PMID: 22323375 BACKGROUND

• 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.

  PMID: 22680789 BACKGROUND

• 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.

  PMID: 29220110 DERIVED

• 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.

  PMID: 26940689 DERIVED

Related Links

• Info of the study

MeSH Terms

Conditions

Neoplasms; Cancer Pain

Interventions

Morphine; Fentanyl; Buprenorphine; Oxycodone

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Codeine

Results Point of Contact

• Title: Dr. Oscar Corli
• Organization: Mario Negri Institution

oscar.corli@marionegri.it

+390239014564

Study Officials

• Oscar Corli, MD

  Mario Negri Institute of Pharmacological Research - IRCCS

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2013
• First Posted: March 12, 2013
• Study Start: April 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 24, 2015
• Results First Posted: November 20, 2015

Record last verified: 2015-10

Locations

IT (9)