CancerPhase 4CERPNCT01809106
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.
A Phase 4 study testing Morphine, Fentanyl and Buprenorphine in people with Cancer and Cancer Pain, run by Mario Negri Institute for Pharmacological Research at 9 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Cancer Pain
- What is being tested?
- Morphine, Fentanyl and Buprenorphine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 518 participants
- Where
- 9 sitesItaly
- Study dates
- Apr 2011to Oct 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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;
Show all 14Show fewer
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Italy9 sites
Ospedale S. Marta
Catania, Italy
Fondazione IRCCS - Istituto Nazionale dei Tumori
Milan, Italy
Istituto Scientifico San Raffaele
Milan, Italy
Azienda Ospedaliera Valtellina-Valchiavenna
Morbegno, Italy
Ospedale Civile di Piacenza
Piacenza, Piacenza, 29100
Arcispedale S. Maria Nuova Azienda Ospedaliera
Reggio Emilia, RE, 42100
Multimedica
Sesto San Giovanni, Italy
Ospedale Gradenigo
Torino, Italy
Ospedale San Giovanni Battista di Torino
Torino, Torino, 10126
About this study
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
- Being tested
- Morphine, Fentanyl, Buprenorphine, Oxycodone
- Keywords
- cancer pain, major opioid, analgesics
- Medical subject headings
- Neoplasms, Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
60 mg /24 ore
FentanylDrug
25 microg/h
BuprenorphineDrug
35 microg/h
OxycodoneDrug
40 mg /24 ore
| Study group | Role | What they receive |
|---|---|---|
| Morphine | Active comparator | Not described Receives: Drug: Morphine |
| Oxycodone | Experimental | Not described Receives: Drug: Oxycodone |
| Buprenorphine | Experimental | Not described Receives: Drug: Buprenorphine |
| Fentanyl | Experimental | Not described Receives: Drug: Fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (1)
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).
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2013 (estimated)
- Study startApr 2011
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 518 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Oscar Corli, MD, Principal investigator, Mario Negri Institute of Pharmacological Research - IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01809106
- Sponsor's protocol ID
- Studio CERP
- Acronym
- CERP
- Status last verified
- Oct 2015
- First submitted
- 8 Mar 2013
- Last updated
- 24 Dec 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 16457716Apolone 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.
PubMed 19401688Greco 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.
PubMed 20842024Apolone 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.
PubMed 22323375Corli 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.
PubMed 22680789Corli O, Caldirola L, Galli F, Torri V, Garattini S, Rulli E, Apolone G. Analgesic efficacy in women and men with cancer pain, treated with strong opioids: are there differences? BMJ Oncol. 2026 Apr 2;5(1):e001024. doi: 10.1136/bmjonc-2025-001024. eCollection 2026.
PubMed 41948194Corli 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.
PubMed 29220110Corli 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.
PubMed 26940689
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01809106
- Acronym / sponsor ID
- CERP / Studio CERP
- Conditions
- Cancer, Cancer Pain
- Keywords
- cancer pain, major opioid, analgesics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 518 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 12 Mar 2013 (estimated)
- Results
- Posted 20 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Morphine | Active comparator | Drug: Morphine |
| Oxycodone | Experimental | Drug: Oxycodone |
| Buprenorphine | Experimental | Drug: Buprenorphine |
| Fentanyl | Experimental | Drug: Fentanyl |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Morphine60 mg /24 ore | Drug | Morphine |
| Fentanyl25 microg/h | Drug | Fentanyl |
| Buprenorphine35 microg/h | Drug | Buprenorphine |
| Oxycodone40 mg /24 ore | Drug | Oxycodone |
Primary outcome
Proportion of Non-Responder (NR) Participants
Time frame: 28 days
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.
1 secondary outcome
Proportion of Full-responder
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16457716Apolone 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.
- Background: PubMed 19401688Apolone 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.
- Background: PubMed 20842024Greco 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.
- Background: PubMed 22323375Apolone 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.
- Background: PubMed 22680789Corli 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.
- Derived from this study: PubMed 41948194Corli O, Caldirola L, Galli F, Torri V, Garattini S, Rulli E, Apolone G. Analgesic efficacy in women and men with cancer pain, treated with strong opioids: are there differences? BMJ Oncol. 2026 Apr 2;5(1):e001024. doi: 10.1136/bmjonc-2025-001024. eCollection 2026.
- Derived from this study: PubMed 29220110Corli 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.
- Derived from this study: PubMed 26940689Corli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oscar Corli, MD principal investigator
Mario Negri Institute of Pharmacological Research - IRCCS
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Morphine, Fentanyl and Buprenorphine in people with Cancer and Cancer Pain, run by Mario Negri Institute for Pharmacological Research at 9 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Non-Responder (NR) Participants (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01809106, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2015.