Exploratory Study on the Use of Pregabalin for the Treatment of Taxol Related Arthralgia-Myalgia

NCT02024568 | Unknown Phase 2

• 2 other identifiers: 105/13WS1826148
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Paclitaxel is chemotherapeutic agent used in many of the most common anti-cancer regimens. Its use is frequently associated with moderate to severe muscle and joint pain that may persist for several days after the treatment. This side effect, known as "Arthralgia-Myalgia Syndrome, has a significant impact on the quality of life and functional abilities of those receiving the treatment, and is not alleviated by many of the interventions attempted for that purpose. Sporadic reports suggest that a drug called gabapentin may be effective in the management of this adverse effect. Observations from our practice indicate that pregabalin, which possesses similar biological activity to that of gabapentin, may also be useful in preventing and treating paclitaxel associated myalgia - arthralgia. The current study represents an initial evaluation of the hypothesis that pregabalin may be beneficial in the management of the symptoms due to the "Arthralgia-Myalgia Syndrome". The investigation will be carried out in the format of a small scale, randomized, placebo controlled trial with patients receiving paclitaxel in the course of standard treatment for breast cancer.

Conditions

Taxane; Drug-related Side Effects and Adverse Reactions; Pain; Breast Cancer

Keywords

Pregabalin; Arthralgia Myalgia Syndrome; Paclitaxel; Pain management; Breast cancer

Outcome Measures

Primary Outcomes (1)

• Integrated Numeric Pain Scores and Rescue Analgesic Medication Requirement as calculated by the method proposed by Silverman et al (Silverman, O'Connor et al. 1993).

  Modern pain research acknowledges the subjective and complex nature of pain that complicates its assessment. Furthermore, ethical imperatives place constraints on the comparative control to serve the in evaluation of a novel analgesic intervention (Silverman, O'Connor et al. 1993). One of the solutions to this issue, using normalized ordinal evaluations of pain and analgesic drug consumption around a central value in a manner that also accounts for changes in analgesic drug requirements (Silverman, O'Connor et al. 1993) will serve for direct assessment of the study hypothesis.

  16 months from study initiation

Secondary Outcomes (3)

• Numeric Pain Score (NPS)

  8 days after receiving cycle of paclitaxel

• The additional number of hours spent in horizontal position (∆HHP**)

  8 days after receiving cycle of paclitaxel

• FACT-taxane score

  On day of recruitment to active phase + one week after 4th cycle of paclitaxel since recruitment to active phase.

Study Arms (2)

Pregabalin

ACTIVE COMPARATOR

Includes 19 out of 38 subjects reporting athralgia-myalgia in the wake of paclitaxel infusion in the course of breast cancer treatment. Pregabalin started on the evening before receiving infusion of paclitaxel and 5 day thereafter. Initial dosing of 75mg twice daily (morning + evening). Option for dose increase with additional 75mg in case of inadequate pain control. A minimal interval of 2 hours is required between doses. In case of poorly tolerated side effects a reduction to 50mg doses is available. Access to additional analgesic interventions is open as required for patient wellbeing.

Drug: Pregabalin

Placebo

PLACEBO COMPARATOR

Includes 19 out of 38 subjects reporting athralgia-myalgia in the wake of paclitaxel infusion in the course of breast cancer treatment. Placebo externally identical to the pregabalin 75mg capsules will be started on the evening before receiving infusion of paclitaxel and 5 day thereafter. Initial dosing of 1 capsule twice daily (morning + evening). Option for dose increase with additional capsule in case of inadequate pain control. A minimal interval of 2 hours is required between doses. In case of poorly tolerated side effects a reduction to capsules with the appearance of 50mg pregabalin capsules is available. Access to additional analgesic interventions is open as required for patient wellbeing.

Drug: Placebo

Interventions

Pregabalin DRUG

See arm description

Also known as: Lyrica

Pregabalin

Placebo DRUG

See arm description

Placebo

Eligibility Criteria

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

You may qualify if:

• Fulfillment of screening criteria.
• Experience of myalgia-arthralgia related pain of moderate or worse degree of severity after a course of paclitaxel containing chemotherapy.

You may not qualify if:

• Ongoing treatment with pregabalin or gabapentin.
• Known restricting adverse events related to treatment with pregabalin or gabapentin.
• Renal failure with GFR less than 30ml/min.
• Participation in clinical trial 3 weeks or less prior to screening.
• Confounding myalgia and / or arthralgia unrelated to chemotherapy.
• Medical condition compromising the likelihood of completing the trial.

Sponsors & Collaborators

• Assaf-Harofeh Medical Center: lead

Study Sites (1)

Assaf HaRofeh Medical Center

Be'er Ya'akov (Zerifin), 7030000, Israel

Location

Related Publications (14)

• Bryans JS, Wustrow DJ. 3-substituted GABA analogs with central nervous system activity: a review. Med Res Rev. 1999 Mar;19(2):149-77. doi: 10.1002/(sici)1098-1128(199903)19:23.0.co;2-b.

  PMID: 10189176 BACKGROUND

• Cella D, Peterman A, Hudgens S, Webster K, Socinski MA. Measuring the side effects of taxane therapy in oncology: the functional assesment of cancer therapy-taxane (FACT-taxane). Cancer. 2003 Aug 15;98(4):822-31. doi: 10.1002/cncr.11578.

  PMID: 12910528 BACKGROUND

• Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measures. Pain. 2000 Dec 1;88(3):287-294. doi: 10.1016/S0304-3959(00)00339-0.

  PMID: 11068116 BACKGROUND

• Forsyth PA, Balmaceda C, Peterson K, Seidman AD, Brasher P, DeAngelis LM. Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing. J Neurooncol. 1997 Oct;35(1):47-53. doi: 10.1023/a:1005805907311.

  PMID: 9266440 BACKGROUND

• Gajraj NM. Pregabalin for pain management. Pain Pract. 2005 Jun;5(2):95-102. doi: 10.1111/j.1533-2500.2005.05205.x.

  PMID: 17177755 BACKGROUND

• Gajraj NM. Pregabalin: its pharmacology and use in pain management. Anesth Analg. 2007 Dec;105(6):1805-15. doi: 10.1213/01.ane.0000287643.13410.5e.

  PMID: 18042886 BACKGROUND

• Garrison JA, McCune JS, Livingston RB, Linden HM, Gralow JR, Ellis GK, West HL. Myalgias and arthralgias associated with paclitaxel. Oncology (Williston Park). 2003 Feb;17(2):271-7; discussion 281-2, 286-8.

  PMID: 12632867 BACKGROUND

• Harmark L, van Puijenbroek E, Straus S, van Grootheest K. Intensive monitoring of pregabalin: results from an observational, Web-based, prospective cohort study in the Netherlands using patients as a source of information. Drug Saf. 2011 Mar 1;34(3):221-31. doi: 10.2165/11585030-000000000-00000.

  PMID: 21332246 BACKGROUND

• Loprinzi CL, Maddocks-Christianson K, Wolf SL, Rao RD, Dyck PJ, Mantyh P, Dyck PJ. The Paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J. 2007 Nov-Dec;13(6):399-403. doi: 10.1097/PPO.0b013e31815a999b.

  PMID: 18032978 BACKGROUND

• Nguyen VH, Lawrence HJ. Use of gabapentin in the prevention of taxane-induced arthralgias and myalgias. J Clin Oncol. 2004 May 1;22(9):1767-9. doi: 10.1200/JCO.2004.99.298. No abstract available.

  PMID: 15118009 BACKGROUND

• Rowinsky EK, Chaudhry V, Forastiere AA, Sartorius SE, Ettinger DS, Grochow LB, Lubejko BG, Cornblath DR, Donehower RC. Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting. J Clin Oncol. 1993 Oct;11(10):2010-20. doi: 10.1200/JCO.1993.11.10.2010.

  PMID: 7692001 BACKGROUND

• Saibil S, Fitzgerald B, Freedman OC, Amir E, Napolskikh J, Salvo N, Dranitsaris G, Clemons M. Incidence of taxane-induced pain and distress in patients receiving chemotherapy for early-stage breast cancer: a retrospective, outcomes-based survey. Curr Oncol. 2010 Aug;17(4):42-7. doi: 10.3747/co.v17i4.562.

  PMID: 20697513 BACKGROUND

• Silverman DG, O'Connor TZ, Brull SJ. Integrated assessment of pain scores and rescue morphine use during studies of analgesic efficacy. Anesth Analg. 1993 Jul;77(1):168-70. No abstract available.

  PMID: 8317727 BACKGROUND

• Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007 Feb;73(2):137-50. doi: 10.1016/j.eplepsyres.2006.09.008. Epub 2006 Nov 28.

  PMID: 17126531 BACKGROUND

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions; Pain; Breast Neoplasms; Myotoxicity; Agnosia

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Pathologic Processes; Radiation Injuries; Wounds and Injuries; Perceptual Disorders; Neurobehavioral Manifestations

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Jonathan Grunfeld, M.D.

  Employee of Asaf Harofeh M.C.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan Grunfeld, M.D.

CONTACT

++972-(0)57-7346453; grunfeldj@asaf.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 31, 2013
• Study Start: December 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: May 1, 2015
• Last Updated: December 31, 2013

Record last verified: 2013-12

Locations

IL (1)