Summary

This phase II randomized trial studies how well bupropion hydrochloride works in improving sexual desire in women with breast or gynecological cancer. Bupropion hydrochloride may work by boosting sexual desire, energy, or motivation without causing intolerable or undesirable side effects.

Objectives

PRIMARY OBJECTIVES:
I. Measure the ability of two dose levels of bupropion hydrochloride (bupropion), 150 or 300 mg of extended release, to improve sexual desire more than a placebo at 9 weeks (8 weeks on the target dose) as measured by the desire subscale of the female sexual function index (FSFI).

SECONDARY OBJECTIVES:
I. Evaluate the side effects of 150 and 300 mg bupropion extended release and differentiate these side effects from those observed in the placebo arm.
II. Evaluate the effect of 150 and 300 mg of bupropion extended release on the Patient Reported Outcomes Measurement Information System (PROMIS) fatigue scale, PROMIS sexual desire and satisfaction measure, patient health questionnaire (PHQ)-4, and the FSFI total score, at 5 and 9 weeks, as well as the desire subscale score of the FSFI at 5 weeks.
III. Evaluate the effect of 150 and 300 mg of bupropion extended release on the global impression of change scale and the patient’s perception of risk versus (vs.) benefit at 5 weeks (4 weeks at target dose) and 9 weeks (8 weeks at target dose).

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive bupropion hydrochloride orally (PO) once daily (QD) on days 1-63 and placebo PO QD on days 8-71.

ARM B: Patients receive bupropion hydrochloride PO QD on days 1-7 and 64-71, and twice daily (BID) on days 8-63.

ARM C: Patients receive placebo PO QD on days 1-7 and 64-71, and BID on days 8-63.

Eligibility

1. PRIOR TO STEP 1 REGISTRATION
2. Score of < 9 on the PHQ-4
3. Patients must have a FSFI desire subscale baseline score less than 3.3 * NOTE-Both the PHQ4 and FSFI must be completed by the patient and data entered in Oncology Patient Enrollment Network (OPEN) at Step 1 registration to determine eligibility within 10 days prior to registration; both of these scores will be calculated in the OPEN system once submitted as part of Step 1 registration; an error message will appear once the patient begins Step 2 registration if one or both of the scores make the patient ineligible; in this situation, continue to complete Step 2 with the reason the patient will not continue on the study as “Other” and specify ineligible
4. Diagnosis of breast or gynecologic cancer, all types (examples are ductal carcinoma in situ [DCIS], lobular carcinoma in situ[LCIS], invasive breast, ovarian, endometrial, vulvar, cervical and vaginal)
5. Completed definitive therapy consisting of surgery, chemotherapy or radiation therapy at least 180 days ago (may continue on Herceptin or endocrine therapy)
6. Post-menopausal as defined by at least ONE of the following: * 12 months (365 days) without a period; * Bilateral oophorectomy; * Chemically induced menopause as long as there are no plans to stop during the study; * For women 57 and under, if at least one ovary and woman has had hysterectomy, must have follicle stimulating hormone (FSH) (> 30 mIU/mL) and estradiol in menopausal range per institution’s laboratory (< 10 for ultra sensitive assay: < 25-30 otherwise); (Note: women 58 and older do not have to have hormonal tests) * At least one ovary intact, with a uterus, and 180 days without a period with FSH (> 30 mIU/mL) and estradiol in menopausal range per institution’s laboratory (generally that is < 10 for ultra sensitive assay: < 25-30 otherwise) (Note: women 58 and older do not have to have hormonal tests)
7. History, physical and performance status of 2 or less within 180 days prior to registration
8. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
9. Total bilirubin =< 1.5 x ULN
10. Glomerular filtration rate > 60ml/min; OR =< ULN creatinine per institution normals
11. For breast cancer patients only, endocrine therapies are allowed (such as aromatase inhibitors, but not current tamoxifen. Prior tamoxifen is permitted with a 30 day wash out period)
12. Vaginal estrogen is allowed, for all protocol disease sites, if dose equal to or less than that in estring (< 7.5 mcg) and it has been used for at least 30 days with no plans to stop or alter use during the course of the study
13. Antidepressants for mood and hot flashes, including selective serotonin reuptake inhibitors (SSRI’s) will be allowed if patients have been on a stable dose for the last 60 days and the dose is not expected to change during the course of the study; only subthreshold or low dose antidepressants will be allowed, not antidepressants that have been titrated up to the highest doses for depression management (i.e. Effexor 37.5 -75 mg or Lexapro 5-10 mg or Celexa 10 – 20 mg)
14. The patient must provide study-specific informed consent prior to study entry/screening
15. Women who report that their motivation/desire for sexual intimacy has decreased since her cancer diagnosis
16. Able to swallow whole capsules
17. Proficient in English (due to number of questionnaires not validated in other languages)
18. Completion of the FSFI and PHQ4; both questionnaires will be required and data entered at the time of step 1 registration
19. PRIOR TO STEP 2 RANDOMIZATION
20. Completion of the following baseline quality of life forms: PHQ4, FSFI, PROMIS sexual function and satisfaction, PROMIS fatigue short form 8a, impact of treatment scale, patient reported outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) items, and revised dyadic adjustment scale; these quality of life forms will be required and data must be entered in RAVE at step 2 registration; if available at the time of step 1 registration, step 2 registration can take place immediately after step 1, but cannot occur more than 30 days after step 1; women who do not currently have a partner do not have to complete the revised dyadic adjustment scale; enter “no partner” for this form