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Auranofin and Sirolimus in Treating Participants With Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT03456700
Recruitment Status : Active, not recruiting
First Posted : March 7, 2018
Results First Posted : July 2, 2020
Last Update Posted : July 2, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Ovarian Serous Tumor Recurrent Ovarian Carcinoma Drug: Auranofin Other: Laboratory Biomarker Analysis Drug: Sirolimus Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial to Evaluate the Efficacy of Auranofin and Sirolimus in Serous Ovarian Cancer Patients With Recurrent Disease
Actual Study Start Date : March 30, 2018
Actual Primary Completion Date : July 31, 2019
Estimated Study Completion Date : March 15, 2023


Arm Intervention/treatment
Experimental: Treatment (auranofin, 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.
Drug: Auranofin
Given PO
Other Name: Ridaura

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Sirolimus
Given PO
Other Names:
  • AY 22989
  • RAPA
  • Rapamune
  • Rapamycin
  • SILA 9268A
  • WY-090217




Primary Outcome Measures :
  1. Number of Participants With a Confirmed Tumor Response (Partial Response [PR] or Complete Response [CR] at Least 4 Weeks Apart) [ Time Frame: 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 :
  1. 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 [ Time Frame: 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.

  2. Progression-free Survival (PFS) [ Time Frame: 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.

  3. Overall Survival (OS) [ Time Frame: 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.

  4. Number of Participants Experiencing at Least One Grade 3 or Worse Adverse Event (AE) [ Time Frame: 1 year 4 months ]
    The outcome measure is the number of participants experiencing at least one grade 3 or worse adverse event (AE).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03456700


Locations
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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Aminah Jatoi Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Mayo Clinic:
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT03456700    
Other Study ID Numbers: MC1761
NCI-2018-00321 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1761 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: March 7, 2018    Key Record Dates
Results First Posted: July 2, 2020
Last Update Posted: July 2, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sirolimus
Auranofin
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents