Ovarian Serous Tumor, Recurrent Ovarian Carcinoma
Conditions
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.
Interventions
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Auranofin, Sirolimus) Participants receive 6 mg auranofin PO QD and 5 mg sirolimus PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Auranofin, Sirolimus) |
|---|---|
| Age, Continuous | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Received prior chemotherapy for this cancer | 20 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 0 Participants |
| Tumor Over-expression of Protein Kinase C (PKC) iota | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 21 |
| other Total, other adverse events | 20 / 21 |
| serious Total, serious adverse events | 9 / 21 |
Outcome results
Primary
Number of Participants With a Confirmed Tumor Response (Partial Response [PR] or Complete Response [CR] at Least 4 Weeks Apart)
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.
Time frame: 1 year 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Auranofin, Sirolimus) | Number of Participants With a Confirmed Tumor Response (Partial Response [PR] or Complete Response [CR] at Least 4 Weeks Apart) | 0 Participants |
Secondary
Number of Participants Experiencing at Least One Grade 3 or Worse Adverse Event (AE)
The outcome measure is the number of participants experiencing at least one grade 3 or worse adverse event (AE).
Time frame: 1 year 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Auranofin, Sirolimus) | Number of Participants Experiencing at Least One Grade 3 or Worse Adverse Event (AE) | 13 Participants |
Secondary
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
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.
Time frame: 1 year 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Auranofin, Sirolimus) | 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 | 0 Participants |
Secondary
Overall Survival (OS)
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.
Time frame: 1 year 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Auranofin, Sirolimus) | Overall Survival (OS) | 4.4 months |
Secondary
Progression-free Survival (PFS)
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.
Time frame: 1 year 4 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Auranofin, Sirolimus) | Progression-free Survival (PFS) | 2.1 months |