Bupropion Hydrochloride in Improving Sexual Desire in Women With Breast or Gynecologic Cancer

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.

Inclusion Criteria:

- PRIOR TO STEP 1 REGISTRATION

- Score of < 9 on the PHQ-4

- 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

- Diagnosis of breast or gynecologic cancer (examples are DCIS, LCIS, invasive breast,
ovarian, endometrial, vulvar, cervical and vaginal)

- Completed definitive therapy consisting of surgery, chemotherapy or radiation therapy
at least 180 days ago (may continue on Herceptin or endocrine therapy)

- Post menopausal as defined by at least ONE of the following:

- 12 months (365 days) without a period,

- Bilateral oophorectomy,

- For woment 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);

- At least one ovary intact and 180 days without a period with 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.

- History, physical and performance status of 2 or less within 180 days prior to
registration

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
limit of normal (ULN)

- Total bilirubin =< 1.5 x ULN

- Glomerular filtration rate > 90ml/min

- 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). )

- 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

- Antidepressants for mood and hot flashes, including 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 (e.g. Effexor up to 75 mg or Lexapro 5-10 mg or Celexa 10- 20 mg)

- The patient must provide study-specific informed consent prior to study
entry/screening

- Women who report that their motivation/desire for sexual intimacy has decreased since
her cancer diagnosis

- Able to swallow whole capsules

- Proficient in English (due to number of questionnaires not validated in other
languages)

- Completion of the FSFI and PHQ4; both questionnaires will be required and data entered
at the time of step 1 registration

- PRIOR TO STEP 2 RANDOMIZATION

- 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; women who do not currently have a partner do not have to complete the revised
dyadic adjustment scale; enter "no partner" for this form

Exclusion Criteria:

- Untreated depression, major depressive disorder (MDD), suicidal ideations or anxiety
disorders in the past 5 years per the medical chart based on Diagnostic and
Statistical Manual (DSM) IV diagnoses

- Seizure disorders

- Current or history of anorexia or bulimia in the past 5 years

- Allergy to bupropion

- Use of drugs metabolized by CYP2D6

- Stage IV cancer

- History of Parkinson's disease, multiple sclerosis or fibromyalgia

- Extensive pelvic exenteration surgery, surgeries which include partial or total
vaginectomy with or without reconstruction; radical vulvectomy with or without remove
of clitoris

- Women who are currently undergoing or planning to undergo reconstruction surgery
during the course of the study; women who have completed reconstruction surgery must
be 30 days from surgery

- Oral or transdermal estrogen therapy is not allowed

- Males are not permitted to participate

- Patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates,
and antiepileptic drugs after chronic use

- Patients who discontinue monoamine oxidase (MAO)-inhibitor (I)'s within 14 days prior
to starting the investigational drug

- Poorly controlled hypertension (systolic blood pressure [BP] >= 160 mmHg or diastolic
BP >= 100 mmHg) on three or more readings in the past 12 months

- Patients with active bipolar disorder

- Patients with impaired decision making as determined by the treating physician

- Concurrent use of bupropion

- Concomitant invasive malignancy requiring treatment other than non-melanomatous skin
cancer.

- Previous or concurrent use of flibanserin.