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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Pain; Breast Carcinoma; Peripheral Neuropathy
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Placebo; Other: Questionnaire Administration; Drug: Minocycline Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Pismo Beach, California, United States, 93449
      • PCR Oncology
  • Illinois
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare-Community Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium NCORP
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium
  • New York
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Oncology Specialists
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Minocycline Hydrochloride; Given PO; Other Names: Minocin; Dynacin; Minomax; Minomycin; Vectrin; Tri-minocycline
Placebo Comparator: Arm II (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.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Other: Questionnaire Administration; Ancillary studies

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Academic and Community Cancer Research United
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles Loprinzi, Academic and Community Cancer Research United

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): July 8, 2016
• Study Completion (Actual): July 8, 2016

Study Registration Dates

• First Submitted: November 14, 2014
• First Submitted That Met QC Criteria: November 20, 2014
• First Posted (Estimate): November 21, 2014

Study Record Updates

• Last Update Posted (Actual): January 31, 2022
• Last Update Submitted That Met QC Criteria: January 28, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Breast Diseases; Neuromuscular Diseases; Breast Neoplasms; Peripheral Nervous System Diseases; Acute Pain; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: RU221408I (Other Identifier: Academic and Community Cancer Research United); P30CA015083 (U.S. NIH Grant/Contract); NCI-2016-01592 (Registry Identifier: CTRP (Clinical Trial Reporting Program))