D-cycloserine in the Management of Chemotherapy-Induced Peripheral Neuropathic Pain

Study Overview
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Brief Summary
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D-cycloserine may help lessen pain and other symptoms of peripheral neuropathy caused by chemotherapy. It is not yet known whether D-cycloserine is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy. This randomized, double-blind, placebo-controlled clinical trial was designed to study D-cycloserine at 2 different doses to see how well each works compared to the other and to a placebo in treating cancer patients with peripheral neuropathy caused by chemotherapy.

Detailed Description
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This is a randomized, double-blind, placebo-controlled study. Initially, patients were randomized to 1 of 2 treatment arms (D-cycloserine 250 mg twice daily or placebo twice daily), and treated for up to 4 weeks in the absence of unacceptable toxicity. Later, the design was changed to randomize patients to 1 of 3 arms as follows: D-cycloserine 50 mg twice daily for up to 12 weeks D-cycloserine 200 mg twice daily for up to 12 weeks Placebo twice daily for up to 12 weeks

Official Title
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A Phase III Study of D-Cycloserine in the Management of Paclitaxel-Induced Peripheral Neuropathic Pain in Breast Cancer Patients

Conditions
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Neurotoxicity, Pain, Breast Cancer

Intervention / Treatment
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* Drug: D-cycloserine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be at least 18 years of age. Patients will be experiencing moderate to severe peripheral neuropathic pain Patients may be on chronic adjuvant pain medications such as antidepressants but must be on stable doses for at least one week prior to admission. Patients may be taking concurrent opioids but they must be willing to allow us to monitor their opioid use while on the trial. Patients must have chronic peripheral neuropathic pain will be defined as pain of 3 or more months duration which began in association with chemotherapy. Patient's will have bilateral peripheral neuropathic pain symptoms primarily involving the feet Patients must have breast cancer (any stage) Patients must be able to read and speak English and provide informed consent. Patients may be receiving chemotherapy as long as the agents are not known to cause a peripheral neuropathy. Patients must have an ECOG Performance Status < 3 and be able to attend the physician study visits Patients must not concurrently use gabapentin or pregabalin or must be willing to wean off their anti-convulsant medications prior to starting the trial. Patients may have diabetes mellitus (type 1 or 2) as long as there is no preexisting neuropathy. Exclusion criteria: Patients will not have secondary cause of neuropathic pain including: HIV/AIDS,traumatic injury, or a personal history of non chemotherapy-induced neuropathy. Patients will not have a history of major depression or severe anxiety. Women of childbearing age will agree to take measures to prevent pregnancy and will not breast-feed while on the study medication. Women who are currently pregnant will not be invited to participate in this study. Patients will not have a history of seizures. Patients cannot be currently receiving antibiotic therapy for tuberculosis (e.g. isoniazid).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (original version)<br>Placebo administered orally twice per day for 4 weeks. | Other: Placebo<br> <br> |
| Active Comparator: D-cycloserine 200mg<br>D-cycloserine administered orally at a dose of 200 mg twice per day for 12 weeks. | Drug: D-cycloserine<br> <br> * Other names: Cycloserine; Seromycin™;|
| Active Comparator: D-cycloserine 50 mg<br>D-cycloserine administered orally at a dose of 50 mg twice per day for 12 weeks. | Drug: D-cycloserine<br> <br> * Other names: Cycloserine; Seromycin™;|
| Active Comparator: D-cycloserine 250mg<br>This was the original active comparator arm (before the design was changed): D-cycloserine administered orally at a dose of 250 mg twice per day for 4 weeks. | Drug: D-cycloserine<br> <br> * Other names: Cycloserine; Seromycin™;|
| Placebo Comparator: Placebo (revised version)<br>Placebo administered orally twice per day for 12 weeks. | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Patient-reported Pain Intensity Scores Between the 3 Arms After the Treatment Period Using the Brief Pain Inventory | Compare patient-reported pain intensity scores after the treatment period (12 weeks) between the 3 arms of the trial. | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Individual Patients' Self-reported Overall Pain Relief Scores Before and After the Treatment Period | Compare individual patients' self-reported pain relief scores before and after the treatment period. | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | 
| Change in Neuropathic Pain Scores in and Between Study Arms Using the Neuropathic Pain Inventory, the FACT-Taxane, and the Leonard Scale. | Compare changes in neuropathic pain scores within each arm, as well as between the 3 arms of the study. Neuropathic pain will be assessed using 3 tools: the Neuropathic Pain Inventory, the FACT-Taxane, and the Leonard Scale. | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | 
| Differences in Pain Interference Between Study Arms Using the Brief Pain Inventory and the FACT-Taxane | Compare the pain interference scores after study treatment between study arms using the brief pain inventory and the FACT-Taxane. | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | 
| Change in the Amount of Opioid Medication Used by Patients in Each Arm Before and After Study Treatment | Record the amount of opioid medication used by patients in each arm before and after the study treatment period. | From the date that the first patient is registered until the last patient completes the 12 weeks of study intervention (approximately 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, neurotoxicity, breast cancer