Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

Study Overview
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Brief Summary
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This randomized clinical trial studies how well minocycline hydrochloride works in reducing chemotherapy induced depression and anxiety in patients with stage I-III breast cancer. Minocycline hydrochloride may prevent changes in memory and thinking and improve the quality of life of breast cancer patients receiving chemotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate anxiety and depression in women with stages I-III breast cancer during the first 8 weeks of doxorubicin-based adjuvant therapy randomized to receive either minocycline (minocycline hydrochloride) or placebo. II. To evaluate markers of neuro-inflammation as assessed by blood based inflammatory cytokines and C11-choline positron emission tomography (PET) in women with stages I-III breast cancer during the first 8 weeks of doxorubicin-based adjuvant therapy randomized to receive either minocycline or placebo. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally (PO) twice daily (BID) for 9 weeks. ARM II: Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks. After completion of study treatment, patients are followed up for 6 months.

Official Title
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Randomized Placebo Controlled Study of Minocycline for Amelioration of Chemotherapy Induced Affective Disorders

Conditions
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Anxiety Disorder, Depression, Recurrent Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Intervention / Treatment
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* Drug: minocycline hydrochloride
* Other: placebo
* Other: laboratory biomarker analysis
* Other: Questionnaire administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed with breast cancer stages I-III initiating first line adjuvant or neoadjuvant doxorubicin hydrochloride (DOX) chemotherapy Postmenopausal defined as amenorrhea > 12 months or follicle stimulating hormone (FSH) and estradiol in institutional postmenopausal range Ability to understand English and read and write at the 8th grade level and give a written informed consent document For additional cohort, women with breast cancer stages I-III who currently on or within 18 months of completing first line adjuvant or neoadjuvant DOX chemotherapy or other chemotherapy for breast cancer. Exclusion Criteria: Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease, with the exception of osteoarthritis and fibromyalgia Concurrent other malignancy or metastatic malignancy of any kind Reported diagnosis of major depression or anxiety disorder prior to breast cancer (BC) diagnosis Currently prescribed psychotropic medications including anti-depressants Known bleeding disorders History of diabetes mellitus, heart disease or stroke Current use of warfarin or other anticoagulants Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hypertension, or psychiatric illness/social situation that would limit compliance with study requirements Pregnant or nursing women Concurrent use of daily full dose aspirin (>= 325 mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month washout period is required prior to randomization Unable to give informed consent Tetracycline allergy Any contraindication to magnetic resonance imaging (MRI)/PET examination including but not limited to ferromagnetic metal in the body, pacemaker, or severe claustrophobia; (however, this portion is optional and if patient is otherwise eligible, can enroll in study without participating in imaging study)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (minocycline hydrochloride)<br>Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly. | Drug: minocycline hydrochloride<br>* 100 mg bid given by mouth for 9 weeks<br>* Other names: Minomycin;Other: laboratory biomarker analysis<br>* Correlative blood levels for cortisol, high sensitivity c-reactive protein (hs-CRP) and inflammatory factors including but not limited to IL-6, TNF-α, IL-1β, and MCP-1 will also be obtained weekly on protocol.<br>* Other names: Correlative studies;Other: Questionnaire administration<br>* The CES-D and STAI will be administrated weekly.<br>* Other names: Ancillary studies;|
| Placebo Comparator: Arm II (placebo)<br>Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly. | Other: placebo<br>* Placebo given by mouth for 9 weeks<br>* Other names: PLCB;Other: laboratory biomarker analysis<br>* Correlative blood levels for cortisol, high sensitivity c-reactive protein (hs-CRP) and inflammatory factors including but not limited to IL-6, TNF-α, IL-1β, and MCP-1 will also be obtained weekly on protocol.<br>* Other names: Correlative studies;Other: Questionnaire administration<br>* The CES-D and STAI will be administrated weekly.<br>* Other names: Ancillary studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Center for Epidemiological Studies Depression Scale (CES-D) scores | The 95% confidence intervals of the depression change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. | Baseline to 9 weeks | 
| Changes in the State Trait Anxiety Index (STAI) scores | The 95% confidence intervals of the anxiety change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. | Baseline to 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Hamilton Anxiety Rating Scale scores | The 95% confidence intervals of the anxiety change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies. | Baseline to 9 weeks | 
| Changes in Hamilton Rating Scale for Depression scores | The 95% confidence intervals of the depression change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies. | Baseline to 9 weeks | 
| Changes in inflammatory blood markers | Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies. | Baseline to 6 months | 
| Changes in the PET/MRI measures | Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies. | Baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer