Minocycline Hydrochloride in Reducing Chemotherapy-Induced Peripheral Neuropathy and Acute Pain in Patients With Breast Cancer Undergoing Treatment With Paclitaxel

Study Overview
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Brief Summary
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This randomized pilot trial studies how well minocycline hydrochloride works in reducing chemotherapy-induced peripheral neuropathy and acute pain in patients with breast cancer undergoing treatment with paclitaxel. Drugs used in chemotherapy, such as paclitaxel, may cause damage to nerves that result in aches, pains, and tingling or numbness of fingers and toes. Minocycline hydrochloride may help lessen nerve damage from paclitaxel and improve the quality of life in breast cancer patients.

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate whether minocycline hydrochloride (minocycline) can alleviate paclitaxel-induced peripheral neuropathy. II. To estimate whether minocycline can alleviate paclitaxel acute pain syndrome (P-APS). III. To examine the possible relative toxicities related to minocycline therapy in this study situation. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive minocycline hydrochloride orally (PO) twice daily (BID) on days 1-7. Treatment repeats every 7 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive a placebo PO BID on days 1-7. Treatment repeats every 7 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of the study, patients are followed up every month for 6 months.

Official Title
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Pilot Clinical Trial Evaluating the Utility of Minocycline as an Agent to Decrease Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Paclitaxel-Induced Acute Pain Syndrome (P-APS): A Randomized Placebo-Controlled, Double Blind Trial

Conditions
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Acute Pain, Breast Carcinoma, Peripheral Neuropathy

Intervention / Treatment
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* Drug: Minocycline Hydrochloride
* Other: Placebo
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to complete questionnaires by themselves or with assistance Planned paclitaxel at a dose of 80 mg/m2 IV given, in the adjuvant breast cancer (postoperative or neo-adjuvant) setting, every week for a planned course of 12 weeks without any other concurrent cytotoxic chemotherapy (trastuzumab and/or other antibody and/or small molecule treatment is allowed, except for PARP inhibitors) Life expectancy > 6 months Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for women of childbearing potential only (determined per clinician discretion) Exclusion Criteria: Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Previous diagnosis of diabetic neuropathy or peripheral neuropathy from any cause History of allergic or other adverse reactions to minocycline Prior exposure to neurotoxic chemotherapy Diagnosis of fibromyalgia Current or planned use of methoxyflurane, oral contraceptives, isotretinoin, penicillin, or ergot alkaloids History of allergic or other adverse reactions to tetracycline

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 |
| --- | --- |
| Experimental: Arm I (minocycline hydrochloride)<br>Patients receive minocycline hydrochloride PO BID on days 1-7. Treatment repeats every 7 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. | Drug: Minocycline Hydrochloride<br>* Given PO<br>* Other names: Vectrin;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive a placebo PO BID on days 1-7. Treatment repeats every 7 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. | Other: Placebo<br>* Given PO<br>* Other names: sham therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) Per Assessment (aAUCpa) of Average Pain (Item 3 on the Daily Post-Paclitaxel Questionnaire) | Average Area Under the Curve (AUC) per assessment (aAUCpa) of average pain (item 3 on the Daily Post-Paclitaxel Questionnaire; Please rate the same aches/pain by circling the ONE number that best describes your aches/pains on the AVERAGE in the last 24 hours.) over 12 weeks. Scores are reported on a 0-100 scale, where 100=better outcome quality of life (QOL). The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the week-12 assessment. | Up to 12 weeks | 
| Area Under the Curve (AUC) of EORTC CIPN20 Sensory Neuropathy Subscale | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neurophathy Module (EORTC QLQ-CIPN20) Sensory Neuropathy Subscale. The EORTC CIPN20 scoring algorithm was used for the sensory (items 31-36, 39, 40 and 48) subscale scores on a 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the week-12 assessment. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to week-12 are averaged to yield the aAUCpa per patient per subcale. | Up to course 12 | 
| Area Under the Curve (AUC) Per Assessment (aAUCpa) of Fatigue (Item 10 on the Acute Pain Syndrome Summary Questionnaire) | Area Under the Curve (AUC) Per Assessment (aAUCpa) of Fatigue (Item 10 on the Acute Pain Syndrome Summary Questionnaire); Over the past week, did you experience fatigue?) over 12 weeks. Scores are reported on a 0-100 scale, where 100=better outcome quality of life (QOL). The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the week-12 assessment. | Baseline to up to 12 weeks |