Prophylactic Gabapentin for Taxane-Induced Arthralgia and Myalgia Syndrome in Breast Cancer Patients Undergoing Adjuvant Chemotherapy

Primary Prophylactic Gabapentin for Taxane-Induced Arthralgia and Myalgia Syndrome in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Randomized Controlled Trial

Taxane-induced arthralgia and myalgia syndrome (TAMS) is one of the most common side effects of taxane chemotherapy. This prospective randomized controlled trial will evaluate the efficacy of gabapentin administered prophylactically on days -2 to +5 during the taxane-portion of chemotherapy for adjuvant breast cancer patients on reducing TAMS. This will be compared to observation alone.

Study Overview

• Status: Unknown
• Conditions: Arthralgia; Myalgia; Invasive Breast Cancer; Chemotherapeutic Toxicity
• Intervention / Treatment: Drug: Gabapentin 300mg

Detailed Description

The taxanes are a class of anticancer agents that interfere with microtubule disassembly. They have been an integral part of adjuvant breast cancer treatment since the early 2000s. Taxane-induced arthralgia and myalgia syndrome (TAMS) is one of the most common side effects of taxane chemotherapy. It is characterized by muscle and joint pain that often starts 24-48 hours after taxane-based chemotherapy, and lasts for 5-7 days. TAMS can significantly impact the level of functioning and quality of life of early-stage breast cancer patients and can occur in up to 87% of women during their chemotherapy.

Many studies have been conducted looking at medications to prevent TAMS. Unfortunately, these are primarily small retrospective or case series studies, and no standard of care has been established. Results from studies looking at antihistamines, corticosteroids, opioids, amifostine, glutamine, Shakuyaku-Kanzou-to (a Japanese herbal medicine), are conflicting and/or inconclusive.

Gabapentin, a structural analog of gamma amino butyric acid (GABA), is a second-line antiepileptic and is also widely used to treat neuropathic pain syndromes. Many oncologists already use prophylactic gabapentin in an attempt to prevent TAMS, however this is supported primarily by small case series and retrospective data, and is not considered standard of care. Unfortunately, a systemic review found no randomized controlled trial evidence supporting these findings.

This prospective randomized controlled trial will be conducted to evaluate the efficacy of gabapentin administered prophylactically on days -2 to +5 during the taxane-portion of chemotherapy for adjuvant breast cancer patients on reducing TAMS. The hypothesis for this study is that prophylactic gabapentin is more effective than observation in reducing the severity of taxane-induced arthralgias and myalgias syndrome in breast cancer patients undergoing adjuvant chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• English-speaking
• Patients must have histologically confirmed, Stage I-III, breast cancer
• Patient is on an 8-cycle adjuvant anthracycline-cyclophosphamide-taxane containing chemotherapy regimen, and will be starting the taxane-containing portion of chemotherapy within 4 weeks of enrollment.
• Patient has not received prior taxane chemotherapy
• ECOG performance status 0 to 2 (on a scale from 0 to 4, with 0 indicating normal activity, 1 symptomatic but ambulatory self-care possible, 2 ambulatory more than 50% of the time, 3 ambulatory 50% of the time or less and nursing care required, and 4 bedridden and possibly requiring hospitalization)
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients on FEC-D, ACTW, DCx4 chemotherapy.
• Metastatic disease
• Patient currently taking gabapentin or pregabalin for other indications prior to initiating chemotherapy
• Patients concomitantly taking other drugs known to influence GABA (e.g. barbituates, benzodiazepines, nonbenzodiazepines, baclofen)
• Patients using selected analgesics (opioids, acetaminophen, aspirin, NSAIDs) in which the dosages have changed in the 2 weeks prior to starting Taxane chemotherapy, or an analgesic medication was discontinued in the last 2 weeks, or a new analgesic medication was started in the last 2 weeks.
• Patients concomitantly using medical marijuana
• Known restricting adverse events or allergy to gabapentin or pregabalin supplements.
• GFR less than 30ml/min
• Myalgia and/or arthralgia unrelated to chemotherapy, or severe pain syndromes, that could confound the results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observation
Experimental: Prophylactic Gabapentin; Gabapentin at a dose of 300mg three times a day for 2 days before and 5 days after each taxane infusion. Administered orally.	Drug: Gabapentin 300mg; Gabapentin 300mg orally three times a day, from 2 days before to 5 days after taxane infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
"Worst" pain score	Brief Pain Inventory-short form assessment tool	Approximately 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arithmetic mean of the four severity pain score items	Brief Pain Inventory-short form assessment tool	Approximately 8 months
Quality of life and function	FACT-Taxane Scale	Approximately 8 months
Chemotherapy dose reductions, delays, and discontinuation		Approximately 8 months
Incidence and severity of peripheral neuropathy	EORTC-QLQ-CIPN20	Approximately 8 months
Gabapentin-related adverse events		Approximately 8 months
Opioid initiation or modifications		Approximately 8 months

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency

Study record dates

Study Major Dates

• Study Start (Anticipated): July 2, 2018
• Primary Completion (Anticipated): June 30, 2019
• Study Completion (Anticipated): June 30, 2020

Study Registration Dates

• First Submitted: June 12, 2018
• First Submitted That Met QC Criteria: June 12, 2018
• First Posted (Actual): June 25, 2018

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 12, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Breast Diseases; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Breast Neoplasms; Arthralgia; Myalgia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: Gabapentin RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No