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

• ClinicalTrials.gov Identifier: NCT02297412
• Recruitment Status: Completed
• First Posted: November 21, 2014
• Results First Posted: November 7, 2018
• Last Update Posted: January 31, 2022
• Sponsor: Academic and Community Cancer Research United
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Academic and Community Cancer Research United

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Pain; Breast Carcinoma; Peripheral Neuropathy	Drug: Minocycline Hydrochloride; Other: Placebo; Other: Quality-of-Life Assessment; Other: Questionnaire Administration	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: 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
• Study Start Date: November 2014
• Actual Primary Completion Date: July 8, 2016
• Actual Study Completion Date: July 8, 2016

Arms and Interventions

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.	Drug: Minocycline Hydrochloride; Given PO; Other Names: Dynacin; Minocin; Minomax; Minomycin; Tri-minocycline; Vectrin; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies
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: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve (AUC) Per Assessment (aAUCpa) of Average Pain (Item 3 on the Daily Post-Paclitaxel Questionnaire) [ Time Frame: 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.
2. Area Under the Curve (AUC) of EORTC CIPN20 Sensory Neuropathy Subscale [ Time Frame: 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.
3. Area Under the Curve (AUC) Per Assessment (aAUCpa) of Fatigue (Item 10 on the Acute Pain Syndrome Summary Questionnaire) [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

PCR Oncology

Pismo Beach, California, United States, 93449

United States, Illinois

Illinois CancerCare-Community Cancer Center

Normal, Illinois, United States, 61761

Carle Cancer Center

Urbana, Illinois, United States, 61801

United States, Iowa

Siouxland Regional Cancer Center

Sioux City, Iowa, United States, 51101

United States, Michigan

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, United States, 48106

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States, 56303

United States, Nebraska

Missouri Valley Cancer Consortium

Omaha, Nebraska, United States, 68106

United States, New York

Hematology Oncology Associates of Central New York-East Syracuse

East Syracuse, New York, United States, 13057

United States, North Carolina

Novant Health Oncology Specialists

Winston-Salem, North Carolina, United States, 27103

United States, Rhode Island

Women and Infants Hospital

Providence, Rhode Island, United States, 02905

United States, Wisconsin

Marshfield Clinic

Marshfield, Wisconsin, United States, 54449

Sponsors and Collaborators

Academic and Community Cancer Research United

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Charles Loprinzi; Academic and Community Cancer Research United

More Information

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT02297412
• Other Study ID Numbers: RU221408I; NCI-2016-01592 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); RU221408I ( Other Identifier: Academic and Community Cancer Research United ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: November 21, 2014
• Results First Posted: November 7, 2018
• Last Update Posted: January 31, 2022
• Last Verified: January 2022

Additional relevant MeSH terms:

Breast Neoplasms; Peripheral Nervous System Diseases; Acute Pain; Neuromuscular Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Pain; Neurologic Manifestations; Minocycline; Anti-Bacterial Agents; Anti-Infective Agents