Prophylactic Gabapentin for Taxane-Induced Arthralgia and Myalgia Syndrome in Breast Cancer Patients Undergoing Adjuvant Chemotherapy
Primary Purpose
Invasive Breast Cancer, Chemotherapeutic Toxicity, Myalgia
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Gabapentin 300mg
Sponsored by
About this trial
This is an interventional treatment trial for Invasive Breast Cancer
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Prophylactic Gabapentin
Observation
Arm Description
Gabapentin at a dose of 300mg three times a day for 2 days before and 5 days after each taxane infusion. Administered orally.
Outcomes
Primary Outcome Measures
"Worst" pain score
Brief Pain Inventory-short form assessment tool
Secondary Outcome Measures
Arithmetic mean of the four severity pain score items
Brief Pain Inventory-short form assessment tool
Quality of life and function
FACT-Taxane Scale
Chemotherapy dose reductions, delays, and discontinuation
Incidence and severity of peripheral neuropathy
EORTC-QLQ-CIPN20
Gabapentin-related adverse events
Opioid initiation or modifications
Full Information
NCT ID
NCT03566394
First Posted
June 12, 2018
Last Updated
June 12, 2018
Sponsor
British Columbia Cancer Agency
1. Study Identification
Unique Protocol Identification Number
NCT03566394
Brief Title
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
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Unknown status
Study Start Date
July 2, 2018 (Anticipated)
Primary Completion Date
June 30, 2019 (Anticipated)
Study Completion Date
June 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
British Columbia Cancer Agency
4. Oversight
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
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Breast Cancer, Chemotherapeutic Toxicity, Myalgia, Arthralgia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Prophylactic Gabapentin
Arm Type
Experimental
Arm Description
Gabapentin at a dose of 300mg three times a day for 2 days before and 5 days after each taxane infusion. Administered orally.
Arm Title
Observation
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
Gabapentin 300mg
Intervention Description
Gabapentin 300mg orally three times a day, from 2 days before to 5 days after taxane infusion
Primary Outcome Measure Information:
Title
"Worst" pain score
Description
Brief Pain Inventory-short form assessment tool
Time Frame
Approximately 8 months
Secondary Outcome Measure Information:
Title
Arithmetic mean of the four severity pain score items
Description
Brief Pain Inventory-short form assessment tool
Time Frame
Approximately 8 months
Title
Quality of life and function
Description
FACT-Taxane Scale
Time Frame
Approximately 8 months
Title
Chemotherapy dose reductions, delays, and discontinuation
Time Frame
Approximately 8 months
Title
Incidence and severity of peripheral neuropathy
Description
EORTC-QLQ-CIPN20
Time Frame
Approximately 8 months
Title
Gabapentin-related adverse events
Time Frame
Approximately 8 months
Title
Opioid initiation or modifications
Time Frame
Approximately 8 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Prophylactic Gabapentin for Taxane-Induced Arthralgia and Myalgia Syndrome in Breast Cancer Patients Undergoing Adjuvant Chemotherapy
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