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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. (CERP)

Primary Purpose

Cancer, Cancer Pain

Status
Completed
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
Morphine
Fentanyl
Buprenorphine
Oxycodone
Sponsored by
Mario Negri Institute for Pharmacological Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer focused on measuring cancer pain, major opioid, analgesics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Arcispedale S. Maria Nuova Azienda Ospedaliera
  • Ospedale S. Marta
  • Fondazione IRCCS - Istituto Nazionale dei Tumori
  • Istituto Scientifico San Raffaele
  • Azienda Ospedaliera Valtellina-Valchiavenna
  • Ospedale Civile di Piacenza
  • Multimedica
  • Ospedale San Giovanni Battista di Torino
  • Ospedale Gradenigo

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Arm Label

Morphine

Oxycodone

Buprenorphine

Fentanyl

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

Full Information

First Posted
March 8, 2013
Last Updated
November 20, 2015
Sponsor
Mario Negri Institute for Pharmacological Research
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1. Study Identification

Unique Protocol Identification Number
NCT01809106
Brief 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.
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mario Negri Institute for Pharmacological Research

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Cancer Pain
Keywords
cancer pain, major opioid, analgesics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
518 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Morphine
Arm Type
Active Comparator
Arm Title
Oxycodone
Arm Type
Experimental
Arm Title
Buprenorphine
Arm Type
Experimental
Arm Title
Fentanyl
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Morphine
Intervention Description
60 mg /24 ore
Intervention Type
Drug
Intervention Name(s)
Fentanyl
Intervention Description
25 microg/h
Intervention Type
Drug
Intervention Name(s)
Buprenorphine
Intervention Description
35 microg/h
Intervention Type
Drug
Intervention Name(s)
Oxycodone
Intervention Description
40 mg /24 ore
Primary Outcome Measure Information:
Title
Proportion of Non-Responder (NR) Participants
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Proportion of Full-responder
Description
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).
Time Frame
28 days
Other Pre-specified Outcome Measures:
Title
The Opioid Escalation Index
Description
The proportion of subjects with an increase of opioid daily dose > 5% compared with the basal dosage (OEI%).
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oscar Corli, MD
Organizational Affiliation
Mario Negri Institute of Pharmacological Research - IRCCS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arcispedale S. Maria Nuova Azienda Ospedaliera
City
Reggio Emilia
State/Province
RE
ZIP/Postal Code
42100
Country
Italy
Facility Name
Ospedale S. Marta
City
Catania
Country
Italy
Facility Name
Fondazione IRCCS - Istituto Nazionale dei Tumori
City
Milano
Country
Italy
Facility Name
Istituto Scientifico San Raffaele
City
Milano
Country
Italy
Facility Name
Azienda Ospedaliera Valtellina-Valchiavenna
City
Morbegno
Country
Italy
Facility Name
Ospedale Civile di Piacenza
City
Piacenza
ZIP/Postal Code
29100
Country
Italy
Facility Name
Multimedica
City
Sesto San Giovanni
Country
Italy
Facility Name
Ospedale San Giovanni Battista di Torino
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Ospedale Gradenigo
City
Torino
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
16457716
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.
Results Reference
background
PubMed Identifier
19401688
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.
Results Reference
background
PubMed Identifier
20842024
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.
Results Reference
background
PubMed Identifier
22323375
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.
Results Reference
background
PubMed Identifier
22680789
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.
Results Reference
background
PubMed Identifier
29220110
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.
Results Reference
derived
PubMed Identifier
26940689
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.
Results Reference
derived
Links:
URL
http://crc.marionegri.it/cancerpain/
Description
Info of the study

Learn more about this trial

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.

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