Bupropion in Reducing Cancer Related Fatigue in Stage I-III Breast Cancer Survivors

Study Overview
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Brief Summary
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This phase III trial studies how well bupropion works in reducing cancer related fatigue in stage I-III breast cancer survivors. Bupropion is a drug that is used to treat depression, as well as to help people quit smoking. Cancer and its treatment can cause fatigue. Giving bupropion may improve cancer related fatigue in breast cancer survivors.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the efficacy of bupropion hydrochloride controlled-release (bupropion) versus placebo in reducing fatigue in a double-blinded, placebo-controlled, randomized clinical trial of breast cancer survivors with fatigue. SECONDARY OBJECTIVES: I. To assess the efficacy of bupropion versus placebo on depression and quality of life in breast cancer survivors with fatigue. II. To assess the tolerability of bupropion in breast cancer survivors with fatigue. EXPLORATORY OBJECTIVES: I. To assess the efficacy of bupropion versus placebo on symptomatology and cognition in breast cancer survivors with fatigue. II. To explore the effects of bupropion on putative mechanisms of cancer-related fatigue. III. To explore associations of CYP2B6 genotype with bupropion metabolism and changes in fatigue. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive bupropion hydrochloride controlled-release orally (PO) once daily (QD) for up to 13 weeks in the absence of unacceptable toxicity. ARM II: Patients receive placebo PO QD for up to 13 weeks in the absence of unacceptable toxicity.

Official Title
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Randomized Placebo Controlled Trial of Bupropion for Cancer Related Fatigue

Conditions
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Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8

Intervention / Treatment
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* Drug: Bupropion Hydrochloride Controlled-release
* Other: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be at least 18 years of age Be diagnosed with cancer Have stable disease or no evidence of disease Report WORST level of fatigue in the past week as moderate to severe (i.e., a score ≥ 4 on a 0-10 scale, Screening Measures, question 1) Have completed surgery, radiation, and/or systemic intravenous anticancer therapy (e.g., chemotherapy, targeted therapy, immunotherapy) 2 or more months prior to enrollment. Participants currently receiving oral maintenance, targeted, or hormonal therapy are eligible. Participants receiving intravenous supportive therapy (e.g., bisphosphonates) are eligible. Able to read and speak English Currently not be pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception, i.e., abstinence, IUD (intrauterine device), hormonal contraceptive (birth control pills) or barrier method (condoms) prior to study entry and for the duration of study participation Be capable of providing written informed consent Exclusion Criteria: Be receiving intravenous anti-cancer therapy (e.g., intravenous immune checkpoint inhibitor therapy, targeted therapy). Be currently taking any medications that contain bupropion (e.g., Wellbutrin, Forfivo, Aplenzin, or Zyban) Be taking an MAOI, linezolid, or methylene blue within two weeks prior to enrollment Be taking any anti-psychotic medications within a week prior to enrollment Have a history of renal impairment (i.e., glomerular filtration rate < 45) Have a history of cirrhosis (i.e., Child-Pugh score ≥ 5) Have a history of seizures Have a history of bulimia or anorexia nervosa Report a history of sensitivity to bupropion Report an allergy to lactose Have psychiatric or neurological disorder that would interfere with study participation per physician or physician's designee.

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (bupropion hydrochloride controlled-release)<br>Patients receive bupropion hydrochloride controlled-release PO QD for up to 13 weeks in the absence of disease progression or unacceptable toxicity. | Drug: Bupropion Hydrochloride Controlled-release<br>* Given PO<br>* Other names: Zyban;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO QD for up to 13 weeks in the absence of disease progression or unacceptable toxicity. | Other: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Measured by the Fatigue subscale of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue subscale (FFS). Will use analysis of covariance with group as the main factor and baseline FFS as a covariate. | At 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life | Measured by the Total Score of the Functional Assessment Cancer Therapy - General scale (included in the FACIT-F). MPlus will be utilized to estimate the indirect (mediation) and direct effects and to obtain bootstrap-based 95% confidence intervals for these effects. | At 12 weeks | 
| Depression | Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Depression Short Form 8a. MPlus will be utilized to estimate the indirect (mediation) and direct effects and to obtain bootstrap based 95% confidence intervals for these effects. | At 12 weeks |