Clinical trial NCT03566394: Prophylactic Gabapentin for Taxane-Induced Arthralgia and Myalgia Syndrome in Breast Cancer Patients Undergoing Adjuvant Chemotherapy
Official title: Primary Prophylactic Gabapentin for Taxane-Induced Arthralgia and Myalgia Syndrome in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Invasive Breast Cancer
Chemotherapeutic Toxicity
Myalgia
Arthralgia
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
First posted: 2018-06-25
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: "Worst" pain score
timeFrame: Approximately 8 months
Secondary outcomes:
measure: Arithmetic mean of the four severity pain score items
timeFrame: Approximately 8 months
measure: Quality of life and function
timeFrame: Approximately 8 months
measure: Chemotherapy dose reductions, delays, and discontinuation
timeFrame: Approximately 8 months
measure: Incidence and severity of peripheral neuropathy
timeFrame: Approximately 8 months
measure: Gabapentin-related adverse events
timeFrame: Approximately 8 months
measure: Opioid initiation or modifications
timeFrame: Approximately 8 months
Other outcomes:
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