Clinical trial NCT03456700: Auranofin and Sirolimus in Treating Participants With Ovarian Cancer
Official title: Phase II Trial to Evaluate the Efficacy of Auranofin and Sirolimus in Serous Ovarian Cancer Patients With Recurrent Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Serous Tumor
Recurrent Ovarian Carcinoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2018-03-07
Enrollment: 22
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With a Confirmed Tumor Response (Partial Response [PR] or Complete Response [CR] at Least 4 Weeks Apart)
timeFrame: 1 year 4 months
Secondary outcomes:
measure: 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
timeFrame: 1 year 4 months
measure: Progression-free Survival (PFS)
timeFrame: 1 year 4 months
measure: Overall Survival (OS)
timeFrame: 1 year 4 months
measure: Number of Participants Experiencing at Least One Grade 3 or Worse Adverse Event (AE)
timeFrame: 1 year 4 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Aminah Jatoi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rousselle B, Massot A, Privat M, Dondaine L, Trommenschlager A, Bouyer F, Bayardon J, Ghiringhelli F, Bettaieb A, Goze C, Paul C, Malacea-Kabbara R, Bodio E. Conception and Evaluation of Fluorescent Phosphine-Gold Complexes: From Synthesis to in vivo Investigations. ChemMedChem. 2022 Jun 3;17(11):e202100773. doi: 10.1002/cmdc.202100773. Epub 2022 Mar 29.