Trial Outcomes & Findings for Minocycline Hydrochloride in Reducing Chemotherapy-Induced Peripheral Neuropathy and Acute Pain in Patients With Breast Cancer Undergoing Treatment With Paclitaxel (NCT NCT02297412)

Last Updated: 2022-01-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

47 participants

Primary outcome timeframe

Up to 12 weeks

Results posted on

2022-01-31

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	23	24
Overall Study COMPLETED	22	23
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Canceled	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Minocycline Hydrochloride) n=22 Participants 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) n=23 Participants 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.	Total n=45 Participants Total of all reporting groups
Age, Continuous	54.8 years STANDARD_DEVIATION 10.1 • n=5 Participants	55.0 years STANDARD_DEVIATION 11.8 • n=7 Participants	54.9 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: Patients who completed the Daily Post-Paclitaxel Questionnaire item 3 over 12 weeks were included in this analysis.

Outcome measures

Outcome measures
Measure	Arm I (Minocycline Hydrochloride) n=20 Participants 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) n=20 Participants 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.
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 Interval 54.4 to 100.0	84.3 scores on a scale Interval 46.5 to 99.7

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Arm I (Minocycline Hydrochloride) n=21 Participants 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) n=20 Participants 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.
Area Under the Curve (AUC) of EORTC CIPN20 Sensory Neuropathy Subscale	94.1 scores on a scale Interval 58.7 to 100.0	89.4 scores on a scale Interval 68.7 to 98.3

PRIMARY outcome

Timeframe: Baseline to up to 12 weeks

Population: Patients who completed the Acute Pain Syndrome Summary Questionnaire over 12 weeks are included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Arm I (Minocycline Hydrochloride) n=21 Participants 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) n=21 Participants 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.
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 Interval 30.8 to 90.0	59.0 scores on a scale Interval 29.4 to 86.4

Adverse Events

Arm I (Minocycline Hydrochloride)

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Arm II (Placebo)

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (Minocycline Hydrochloride) n=22 participants at risk 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) n=23 participants at risk 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.
Infections and infestations Lung infection	4.5% 1/22 • Number of events 2 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	0.00% 0/23 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Lymphocyte count decreased	9.1% 2/22 • Number of events 2 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	0.00% 0/23 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).

Other adverse events

Additional Information

Charles L. Loprinzi, M.D.

Mayo Clinic

Phone: 507/284-6026

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I (Minocycline Hydrochloride) n=22 participants at risk 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) n=23 participants at risk 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.
Gastrointestinal disorders Abdominal pain	4.5% 1/22 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Diarrhea	4.5% 1/22 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
General disorders Fatigue	9.1% 2/22 • Number of events 3 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	8.7% 2/23 • Number of events 2 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Lymphocyte count decreased	9.1% 2/22 • Number of events 3 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Investigations Neutrophil count decreased	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Metabolism and nutrition disorders Hyponatremia	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	8.7% 2/23 • Number of events 2 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Musculoskeletal and connective tissue disorders Back pain	4.5% 1/22 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	0.00% 0/23 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	8.7% 2/23 • Number of events 10 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Nervous system disorders Dizziness	4.5% 1/22 • Number of events 3 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	0.00% 0/23 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Nervous system disorders Headache	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	8.7% 2/23 • Number of events 3 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	8.7% 2/23 • Number of events 7 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Vascular disorders Hypertension	0.00% 0/22 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	4.3% 1/23 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).
Vascular disorders Thromboembolic event	4.5% 1/22 • Number of events 1 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).	0.00% 0/23 • Up to 12 weeks The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT).