Auranofin and Sirolimus in Treating Participants With Ovarian Cancer

PRIMARY OBJECTIVES:

I. To estimate the overall tumor response rate (ORR, that is, complete response [CR] +
partial response [PR]) of the combination of auranofin and sirolimus in the setting of
metastatic serous ovarian cancer across all patients.

SECONDARY OBJECTIVES:

I. To estimate the overall tumor response rate (ORR, that is, complete response [CR] +
partial response [PR]) of the combination of auranofin and sirolimus in the setting of
metastatic serous ovarian cancer within patients that have overexpression of PKCiota.

II. To estimate progression-free survival, overall survival, and adverse events from the
combination of auranofin and sirolimus.

CORRELATIVE OBJECTIVES:

I. To explore whether PKCiota-relevant biomarkers in serous ovarian cancer tumors are
associated with treatment response patterns, such as ORR, progression free survival, and
overall survival.

OUTLINE:

Participants receive auranofin orally (PO) once daily (QD) and sirolimus PO QD on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, participants are followed up every 6 months for 3 years.

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1

- Ovarian cancer of serous histology

- Incurable cancer

- Willingness to provide paraffin-embedded tissue blocks of ovarian cancer

- Measurable disease

- Obtained =< 14 days prior to registration: Absolute neutrophil count (ANC) >= 1500 uL

- Obtained =< 14 days prior to registration: Platelet (PLT) >= 100,000 uL

- Obtained =< 14 days prior to registration: Hemoglobin (Hgb) >= 9 g/dL

- Obtained =< 14 days prior to registration: Total bilirubin =< 1.5 x upper limit of
normal (ULN) or direct bilirubin =< ULN

- Obtained =< 14 days prior to registration: Serum glutamic-oxaloacetic transaminase
(SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase
(SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN or SGOT (AST) and SGPT (ALT) =< 5 x
ULN is acceptable if liver has tumor involvement

- Obtained =< 14 days prior to registration: Creatinine =< 1.5 x ULN

- Obtained =< 14 days prior to registration: Fasting serum glucose =< 1.5 x ULN

- Obtained =< 14 days prior to registration: Total cholesterol =< 1.5 x ULN

- Obtained =< 14 days prior to registration: Triglycerides =< 1.5 x ULN

- Life expectancy >= 12 weeks

Exclusion Criteria:

- Platinum-sensitive disease (exceptions allowed: patient has had a hypersensitivity
reaction to platinum or the treating oncologist thinks that further platinum therapy
is not in the patient?s best interest)

- Morbidities or concurrent major illness (for example, bowel obstruction or a second
active malignancy) that, in the opinion of the treating healthcare provider, would
make participation in the trial problematic

- Leptomeningeal disease or uncontrolled brain metastasis

- Failure to recover from acute, reversible effects of prior therapy regardless of
interval since last treatment

- NOTE: Patients can have peripheral (sensory) neuropathy

- History of hypertriglyceridemia or hypercholesterolemia and currently on medication(s)

- Use of St. John?s wort =< 7 days prior to registration

- Unable to discontinue use of a strong CYP3A4 inhibitor