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

Phase 2

Completed

Conditions: Acute Pain
Peripheral Neuropathy
Breast Carcinoma

Interventions: Drug: Minocycline Hydrochloride
Other: Placebo
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Registration Number: NCT02297412

Lead Sponsor: Academic and Community Cancer Research United

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (minocycline hydrochloride)	Quality-of-Life Assessment	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.
Arm I (minocycline hydrochloride)	Questionnaire Administration	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.
Arm II (placebo)	Quality-of-Life Assessment	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.
Arm I (minocycline hydrochloride)	Minocycline Hydrochloride	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.
Arm II (placebo)	Placebo	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.
Arm II (placebo)	Questionnaire Administration	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.

Primary Outcome Measures

Name	Time	Method
Area Under the Curve (AUC) Per Assessment (aAUCpa) of Fatigue (Item 10 on the Acute Pain Syndrome Summary Questionnaire)	Baseline to up to 12 weeks	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.
Area Under the Curve (AUC) of EORTC CIPN20 Sensory Neuropathy Subscale	Up to course 12	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.
Area Under the Curve (AUC) Per Assessment (aAUCpa) of Average Pain (Item 3 on the Daily Post-Paclitaxel Questionnaire)	Up to 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (12): Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Marshfield Clinic
🇺🇸
Marshfield, Wisconsin, United States
Hematology Oncology Associates of Central New York-East Syracuse
🇺🇸
East Syracuse, New York, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸
Saint Cloud, Minnesota, United States
Michigan Cancer Research Consortium NCORP
🇺🇸
Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Missouri Valley Cancer Consortium
🇺🇸
Omaha, Nebraska, United States
Novant Health Oncology Specialists
🇺🇸
Winston-Salem, North Carolina, United States
PCR Oncology
🇺🇸
Pismo Beach, California, United States
Illinois CancerCare-Community Cancer Center
🇺🇸
Normal, Illinois, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Women and Infants Hospital
🇺🇸
Providence, Rhode Island, United States