Acute Pain, Breast Carcinoma, Peripheral Neuropathy
Conditions
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.
Interventions
Given PO
OTHERPlacebo
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 22 |
| 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. | 23 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Canceled | 1 | 1 |
Baseline characteristics
| Characteristic | Arm I (Minocycline Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 10.1 | 55.0 years STANDARD_DEVIATION 11.8 | 54.9 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment United States | 22 Participants | 23 Participants | 45 Participants |
| Sex: Female, Male Female | 22 Participants | 23 Participants | 45 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 8 / 22 | 9 / 23 |
| serious Total, serious adverse events | 3 / 22 | 1 / 23 |
Outcome results
Primary
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.
Time frame: Up to course 12
Population: Patients who completed the EORTC Chemotherapy-Induced Peripheral Neurophathy Module Sensory Neuropathy Subscale items over 12 weeks were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Minocycline Hydrochloride) | Area Under the Curve (AUC) of EORTC CIPN20 Sensory Neuropathy Subscale | 94.1 scores on a scale |
| Arm II (Placebo) | Area Under the Curve (AUC) of EORTC CIPN20 Sensory Neuropathy Subscale | 89.4 scores on a scale |
p-value: 0.1146Wilcoxon (Mann-Whitney)
Primary
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.
Time frame: Up to 12 weeks
Population: Patients who completed the Daily Post-Paclitaxel Questionnaire item 3 over 12 weeks were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Minocycline Hydrochloride) | Area Under the Curve (AUC) Per Assessment (aAUCpa) of Average Pain (Item 3 on the Daily Post-Paclitaxel Questionnaire) | 96.0 scores on a scale |
| Arm II (Placebo) | Area Under the Curve (AUC) Per Assessment (aAUCpa) of Average Pain (Item 3 on the Daily Post-Paclitaxel Questionnaire) | 84.3 scores on a scale |
p-value: 0.0186Wilcoxon (Mann-Whitney)
Primary
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.
Time frame: Baseline to up to 12 weeks
Population: Patients who completed the Acute Pain Syndrome Summary Questionnaire over 12 weeks are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Minocycline Hydrochloride) | Area Under the Curve (AUC) Per Assessment (aAUCpa) of Fatigue (Item 10 on the Acute Pain Syndrome Summary Questionnaire) | 76.7 scores on a scale |
| Arm II (Placebo) | Area Under the Curve (AUC) Per Assessment (aAUCpa) of Fatigue (Item 10 on the Acute Pain Syndrome Summary Questionnaire) | 59.0 scores on a scale |
p-value: 0.0243Wilcoxon (Mann-Whitney)