Oxycodone and Pregabalin for the Treatment of Oncological Neuropathic Pain - Full Text View

Sponsors and Collaborators:	Associazione Progetto Oncologia UMAN.A Mario Negri Institute for Pharmacological Research
Information provided by:	Associazione Progetto Oncologia UMAN.A
ClinicalTrials.gov Identifier:	NCT00637975

Purpose

The aim of the study is to assess tolerability and activity of oxycodone and pregabalin in combination for the treatment of oncological neuropathic pain with two different strategies.

Condition	Intervention	Phase
Cancer Pain	Drug: oxycodone Drug: pregabalin	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Oxycodone Pregabalin Oxycodone hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Randomized Phase II Trial Evaluating Activity and Tolerability of Fixed Dose of Oxycodone and Increasing Dose of Pregabalin Versus Increasing Dose of Oxycodone and Fixed Dose of Pregabalin for the Treatment of Oncological Neuropathic Pain

Further study details as provided by Associazione Progetto Oncologia UMAN.A:

Primary Outcome Measures:

Achievement of analgesia (decrease of at least 1/3 of pain intensity) assessed by NRS scale [ Time Frame: within 15 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pain control rate [ Time Frame: within 15 days ] [ Designated as safety issue: No ]
Reduction of Break Through Pain number [ Time Frame: within 15 days ] [ Designated as safety issue: No ]
Record of adverse events [ Time Frame: within 15 days ] [ Designated as safety issue: Yes ]
Reduction of allodynia in patients presenting it at T0 [ Time Frame: within 15 days ] [ Designated as safety issue: No ]
Patient satisfaction [ Time Frame: within 15 days ] [ Designated as safety issue: No ]
Assessing whether COMT and mu blood polymorphisms are associated to response [ Time Frame: within 15 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	September 2007
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental oxycodone 20 mg/day plus pregabalin at increasing dose starting from 50 mg/day for 15 days or until unacceptable toxicity develops	Drug: oxycodone Arm A - 20 mg/day Arm B - increasing dose startnig at 20 mg/day For 15 days or until unacceptable toxicity develops. Drug: pregabalin Arm A - pregabalin at increasing dose starting from 50 mg/day Arm B - pregabalin 50 mg/day For 15 days or until unacceptable toxicity develops.
B: Active Comparator pregabalin 50 mg/day plus oxycodone at increasing dose starting from 20 mg/day. For 15 days or until unacceptable toxicity develops	Drug: oxycodone Arm A - 20 mg/day Arm B - increasing dose startnig at 20 mg/day For 15 days or until unacceptable toxicity develops. Drug: pregabalin Arm A - pregabalin at increasing dose starting from 50 mg/day Arm B - pregabalin 50 mg/day For 15 days or until unacceptable toxicity develops.

Detailed Description:

Neuropathic pain is frequently diagnosed as a complication of cancer pain. While opioids are the mainstay of cancer pain management,their efficacy in neuropathic pain seems to be less then optimal,and adjuvant drugs, mainly anticonvulsants and antidepressants,are often combined with opioids in the analgesic regimen of patients with neuropathic cancer pain. This approach is suggested by well-established guidelines, but the analgesic benefit and the safety of pregabalin and oxycodone in combination is not yet documented. The aim of this study is to assess the activity and tolerability of the addition of pregabalin to oxycodone in the treatment of patients with neuropathic pain due to neoplasm.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

instrumental and clinical diagnosis of every malignant neoplasm
presence of pain with a neuropathic component in the opinion of the physician
presence of pain >=4(NRS)
PS ECOG <3
written informed consent

Exclusion Criteria:

serum creatinine >2mg/ml or creatinine clearance <40 ml/min
mild or severe hepatic insufficiency
iatrogenic neuropathy caused by chemotherapeutic agents
previous allergic reactions to oxycodone and pregabalin
pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00637975

Contacts

Contact: Gabriella Farina, MD	+39 02 6363 2223	gabriella.farina@fbf.milano.it
Contact: Aurora Rizzo, MSD	+39 02 6363 2223	oncologia.ricerca@fbf.milano.it

Locations

Italy
Ospedale Fatebenefratelli	Recruiting
Benevento, Italy, 82100
Contact: Antonio Febbraro, MD +39 3403371731 antoniofebbraro@virgilio.it
Principal Investigator: Antonio Febbraro, MD
Ospedali Riuniti	Not yet recruiting
Bergamo, Italy, 24123
Contact: Roberto Labianca, MD +39 035269111 RLabianca@ospedaliriuniti.bergamo.it
Principal Investigator: Roberto Labianca, MD
Sub-Investigator: Cecilia Moro, MD
Ospedale S. Orsola	Recruiting
Brescia, Italy, 25122
Contact: Giordano Beretta, MD +39 0302971224 gdberetta@fatebenefratelli.it
Principal Investigator: Giordano Beretta, MD
Fatebenefratelli and Ophtalmic Hospital	Recruiting
Milano, Italy, 20121
Contact: Gabriella Farina, MD +39 0263632223 gabriella.farina@fbf.milano.it
Contact: Aurora Rizzo, PharmD +39 0263632223 aurora.rizzo@gmail.com
Principal Investigator: Gabriella Farina, MD
Sub-Investigator: Marina C Garassino, MD
Ospedale Fatebenefratelli	Recruiting
Roma, Italy
Contact: Enrico Breda, MD +39 330291335 enricobreda@libero.it
Principal Investigator: Enrico Breda, MD
Italy, Milano
Ospedale Civile di Legnano	Recruiting
Parabiago, Milano, Italy, 20015
Contact: Elena Collovà, MD +39 3478632345 laelena75@hotmail.com
Sub-Investigator: Elena Collovà, MD
Principal Investigator: Sergio Fava, MD
Ospedale Serbelloni	Recruiting
Gorgonzola, Milano, Italy, 29964
Contact: Luciano Isa, MD +39 0295707207 luciano.isa@aospmelegnano.it
Principal Investigator: Luciano Isa, MD
Sub-Investigator: Claudia Carbone, MD
Italy, Verona
Ospedale Sacro Cuore	Recruiting
Negrar, Verona, Italy, 37024
Contact: Roberto Magarotto, MD +39 0456013111 roberto.magarotto@sacrocuore.it
Sub-Investigator: Roberto Magarotto, MD
Principal Investigator: Marco Venturini, MD
Sub-Investigator: Francesca Coati

Sponsors and Collaborators

Associazione Progetto Oncologia UMAN.A

Mario Negri Institute for Pharmacological Research

Investigators

Principal Investigator:

Gabriella Farina, MD

Fatebenefratelli and Ophtalmic Hospital

More Information

Publications:

Negri E, Bettaglio R, Demartini L, Allegri M, Barbieri M, Miotti D, Paulin L, Buonocore M, Bonezzi C. [Validation of the Italian version of the "Neuropathic Pain Scale" and its clinical applications] Minerva Anestesiol. 2002 Mar;68(3):95-104. Italian.

Riley J, Ross JR, Rutter D, Wells AU, Goller K, du Bois R, Welsh K. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care Cancer. 2006 Jan;14(1):56-64. Epub 2005 Jun 11.

Mucci-LoRusso P, Berman BS, Silberstein PT, Citron ML, Bressler L, Weinstein SM, Kaiko RF, Buckley BJ, Reder RF. Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study. Eur J Pain. 1998;2(3):239-49.

Bruera E, Belzile M, Pituskin E, Fainsinger R, Darke A, Harsanyi Z, Babul N, Ford I. Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. J Clin Oncol. 1998 Oct;16(10):3222-9.

Altier N, Dion D, Boulanger A, Choinière M. Management of chronic neuropathic pain with methadone: a review of 13 cases. Clin J Pain. 2005 Jul-Aug;21(4):364-9.

Gralow I. Cancer pain: an update of pharmacological approaches in pain therapy. Curr Opin Anaesthesiol. 2002 Oct;15(5):555-61.

Farrar JT, Portenoy RK. Neuropathic cancer pain: the role of adjuvant analgesics. Oncology (Williston Park). 2001 Nov;15(11):1435-42, 1445; discussion 1445, 1450-3. Review.

Dirks J, Petersen KL, Rowbotham MC, Dahl JB. Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. Anesthesiology. 2002 Jul;97(1):102-7.

Caraceni A, Zecca E, Bonezzi C, Arcuri E, Yaya Tur R, Maltoni M, Visentin M, Gorni G, Martini C, Tirelli W, Barbieri M, De Conno F. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol. 2004 Jul 15;22(14):2909-17.

Mercadante S, Arcuri E, Tirelli W, Villari P, Casuccio A. Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study. Tumori. 2002 May-Jun;88(3):239-42.

Grond S, Zech D, Diefenbach C, Radbruch L, Lehmann KA. Assessment of cancer pain: a prospective evaluation in 2266 cancer patients referred to a pain service. Pain. 1996 Jan;64(1):107-14.

Portenoy RK, Foley KM, Inturrisi CE. The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. Pain. 1990 Dec;43(3):273-86.

Chua KS, Reddy SK, Lee MC, Patt RB. Pain and loss of function in head and neck cancer survivors. J Pain Symptom Manage. 1999 Sep;18(3):193-202.

Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain. 1995 Oct;63(1):65-76.

Caraceni A. Clinicopathologic correlates of common cancer pain syndromes. Hematol Oncol Clin North Am. 1996 Feb;10(1):57-78. Review.

Elliott KJ. Taxonomy and mechanisms of neuropathic pain. Semin Neurol. 1994 Sep;14(3):195-205. Review. No abstract available.

Kalso E. Oxycodone. J Pain Symptom Manage. 2005 May;29(5 Suppl):S47-56. Review.

Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, Sampaio C, Sindrup S, Wiffen P; EFNS Task Force. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol. 2006 Nov;13(11):1153-69.

Bennett MI, Simpson KH. Gabapentin in the treatment of neuropathic pain. Palliat Med. 2004 Jan;18(1):5-11. Review.

Ross JR, Goller K, Hardy J, Riley J, Broadley K, A'hern R, Williams J. Gabapentin is effective in the treatment of cancer-related neuropathic pain: a prospective, open-label study. J Palliat Med. 2005 Dec;8(6):1118-26.

Frampton JE, Foster RH. Pregabalin: in the treatment of postherpetic neuralgia. Drugs. 2005;65(1):111-8; discussion 119-20. Review.

Davis MP. What is new in neuropathic pain? Support Care Cancer. 2007 Apr;15(4):363-72. Epub 2006 Nov 28. Review.

Sonnett TE, Setter SM, Campbell RK. Pregabalin for the treatment of painful neuropathy. Expert Rev Neurother. 2006 Nov;6(11):1629-35. Review.

Reyes-Gibby CC, Shete S, Rakvåg T, Bhat SV, Skorpen F, Bruera E, Kaasa S, Klepstad P. Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain. 2007 Jul;130(1-2):25-30. Epub 2006 Dec 6.

Simon R, Wittes RE, Ellenberg SS. Randomized phase II clinical trials. Cancer Treat Rep. 1985 Dec;69(12):1375-81.

Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K. The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients. J Palliat Care. 1991 Summer;7(2):6-9.

Caraceni A, Mendoza TR, Mencaglia E, Baratella C, Edwards K, Forjaz MJ, Martini C, Serlin RC, de Conno F, Cleeland CS. A validation study of an Italian version of the Brief Pain Inventory (Breve Questionario per la Valutazione del Dolore). Pain. 1996 Apr;65(1):87-92.

Responsible Party:	Fatebenefratelli and Ophtalmic Hospital ( Gabriella Farina )
Study ID Numbers:	NEUROPAIN01, EudraCT Number 2007-005222-69
Study First Received:	March 12, 2008
Last Updated:	January 29, 2009
ClinicalTrials.gov Identifier:	NCT00637975 History of Changes
Health Authority:	Italy: Ethics Committee; Italy: Ministry of Health; Italy: National Institute of Health; Italy: National Monitoring Centre for Clinical Trials - Ministry of Health; Italy: The Italian Medicines Agency

Keywords provided by Associazione Progetto Oncologia UMAN.A:

neuropathic pain
oxycodone
pregabalin
Patients with cancer and presenting a neuropathic pain

Study placed in the following topic categories:

Oxycodone
Central Nervous System Depressants
Pregabalin
Narcotics
Pain

Peripheral Nervous System Agents
Analgesics
Anticonvulsants
Analgesics, Opioid

Additional relevant MeSH terms:

Oxycodone
Physiological Effects of Drugs
Pregabalin
Central Nervous System Depressants
Narcotics
Pharmacologic Actions
Sensory System Agents

Therapeutic Uses
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Opioid
Anticonvulsants

ClinicalTrials.gov processed this record on May 07, 2009