Auranofin and Sirolimus in Treating Participants With Ovarian Cancer

Phase 2

Terminated

Conditions: Recurrent Ovarian Carcinoma
Ovarian Serous Tumor

Interventions: Drug: Auranofin
Other: Laboratory Biomarker Analysis
Drug: Sirolimus

Registration Number: NCT03456700

Lead Sponsor: Mayo Clinic

Brief Summary: This phase II trial studies how well auranofin and sirolimus work in treating participants with ovarian cancer. Immunosuppressive therapy, such as auranofin and sirolimus, is used to decrease the body?s immune response and may increase blood cell count.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 22

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
Ovarian, Fallopian Tube or Primary Peritoneal 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (auranofin, sirolimus)	Laboratory Biomarker Analysis	Participants receive auranofin PO QD and sirolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Treatment (auranofin, sirolimus)	Auranofin	Participants receive auranofin PO QD and sirolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Treatment (auranofin, sirolimus)	Sirolimus	Participants receive auranofin PO QD and sirolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Confirmed Tumor Response (Partial Response [PR] or Complete Response [CR] at Least 4 Weeks Apart)	1 year 4 months	The outcome measure is the number of participants with a confirmed tumor response (partial response \[PR\] or complete response \[CR\] at least 4 weeks apart). PR and CR are defined using RECIST 1.1 criteria. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target and non-target lesions and normalisation of tumour marker level. Any pathological lymph nodes must have reduction in short axis to \<10 mm.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	1 year 4 months	Overall survival (OS) is defined as the time from registration to death from any cause. OS will be estimated using the method of Kaplan-Meier.
Progression-free Survival (PFS)	1 year 4 months	Progression-free survival (PFS) is defined as the time from registration to the first of either disease progression or death from any cause. Patients who receive the study drug, but then never return for an evaluation will be censored on their last follow-up date. PFS will be estimated using the method of Kaplan-Meier. Progression is defined using RECIST 1.1 criteria; Progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression), Unequivocal progression (see comments below) of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression), or appearance of new malignant lesions.
Number of Participants Experiencing at Least One Grade 3 or Worse Adverse Event (AE)	1 year 4 months	The outcome measure is the number of participants experiencing at least one grade 3 or worse adverse event (AE).
Number of Participants With a Confirmed Tumor Response (PR or CR at Least 4 Weeks Apart) in the Subset of Participants That Have Over-expression of Protein Kinase C (PKC) Iota	1 year 4 months	The outcome measure is the number of participants with a confirmed tumor response (partial response \[PR\] or complete response \[CR\] at least 4 weeks apart) in the subset of participants that have overexpression of PKC iota. PR and CR are defined using RECIST 1.1 criteria. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target and non-target lesions and normalisation of tumour marker level. Any pathological lymph nodes must have reduction in short axis to \<10 mm.