Auranofin + Sirolimus for Ovarian Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: St. John's wort, CYP3A4 inhibitors

Disqualifiers: Platinum-sensitive, Brain metastasis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 28 days per cycle, repeated

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining auranofin and sirolimus in treating ovarian cancer. These drugs aim to suppress the immune response, potentially boosting blood cell counts. The trial seeks participants with ovarian, Fallopian tube, or primary peritoneal cancer that cannot be cured. Participants should have a diagnosis impacting their daily lives and be willing to provide tissue samples for study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications to join the trial?

The trial does not clearly state if you need to stop all current medications, but you cannot use St. John's wort within 7 days before joining, and you must be able to stop using strong CYP3A4 inhibitors. If you have a history of high triglycerides or cholesterol and are on medication for it, you may not be eligible.

Is there any evidence suggesting that auranofin and sirolimus are likely to be safe for humans?

Research has shown that auranofin and sirolimus have been tested together in patients with ovarian cancer. In these studies, most patients tolerated the combination well, but it did not significantly benefit some with recurring ovarian cancer.

While these drugs are being tested for ovarian cancer, they also treat other conditions. For instance, auranofin is already approved for rheumatoid arthritis, indicating its safety for that condition, though its effects may differ when used for cancer.

For those considering joining a trial with these drugs, safety remains a top priority. Trials monitor for serious side effects and ensure any risks are understood and managed. Discussing concerns with the study team can help in making an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for ovarian cancer?

Researchers are excited about the combination of auranofin and sirolimus for ovarian cancer because it targets the disease in a unique way. Auranofin, traditionally used to treat rheumatoid arthritis, works by inhibiting a specific enzyme called thioredoxin reductase, which cancer cells rely on for survival. Sirolimus, on the other hand, blocks a pathway that cancer cells use to grow and divide. This dual approach could potentially overcome resistance seen with current standard chemotherapy options, offering a new hope for patients with ovarian cancer.

What evidence suggests that auranofin and sirolimus might be an effective treatment for ovarian cancer?

Research has shown that the combination of auranofin and sirolimus, which participants in this trial will receive, has not been very effective in treating patients with recurring high-grade serous ovarian cancer. Studies found that patients using this combination lived for about 4.4 months on average and experienced about 2.1 months before the cancer worsened. These results indicate limited success in managing ovarian cancer. Although researchers are exploring auranofin and sirolimus for their potential to reduce immune response, this has not led to significant improvements for ovarian cancer patients so far. ^{1 3 4 6 7}

Who Is on the Research Team?

Aminah Jatoi, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for people with ovarian cancer, including serous cystadenoma, who have measurable disease and a life expectancy of at least 12 weeks. They should be relatively healthy (ECOG score 0 or 1) and have certain blood counts and chemistries within specific ranges. Those with controlled brain metastasis, unresolved effects from past treatments, or sensitive to platinum-based therapies are excluded.

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

Exclusion Criteria

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)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

28 days per cycle, repeated

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 6 months for 3 years.

3 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Auranofin
• Sirolimus

Trial Overview The effectiveness of auranofin and sirolimus in treating ovarian cancer is being tested. These drugs aim to suppress the immune system which might help increase blood cell count in participants with this condition.

How Is the Trial Designed?

Group I: Treatment (auranofin, sirolimus) Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41114938/

A Phase 2 Trial of Protein Kinase C Iota Inhibition With the ... As prescribed here, auranofin and sirolimus manifested no antineoplastic activity in patients with recurrent high-grade serous ovarian ...

2. researchgate.net researchgate.net/publication/396716590_A_Phase_2_Trial_of_Protein_Kinase_C_Iota_Inhibition_With_the_Combination_of_Auranofin_and_Sirolimus_in_Patients_With_Recurrent_Ovarian_Cancer

A Phase 2 Trial of Protein Kinase C Iota Inhibition With the ... Conclusions As prescribed here, auranofin and sirolimus manifested no antineoplastic activity in patients with recurrent high-grade serous ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/00/NCT03456700/Prot_SAP_000.pdf

Mayo Clinic Cancer Center Phase II Trial to Evaluate the Efficacy of Auranofin and Sirolimus in Serous Ovarian Cancer. Patients with Recurrent Disease. Study Chairs: Aminah Jatoi MD.

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/02/NCT01737502/Prot_SAP_000.pdf

MC1125 / 11-001987 A Phase I-II Trial of Combined PKCι ... Based on these data, we are pursuing a phase I/II trial to assess the efficacy of combined chemotherapy using auranofin and the mTOR inhibitor ...

5. mdpi.com mdpi.com/1424-8247/18/11/1628

Repurposing Auranofin for Oncology and Beyond: A Brief ... The median overall survival was 4.4 months (95% Confidence Interval 2.6–12.5 months), and the progression-free survival was 2.1 months, suggesting limited ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03456700

Study Details | NCT03456700 | Auranofin and Sirolimus in ... This phase II trial studies how well auranofin and sirolimus work in treating participants with ovarian cancer. Immunosuppressive therapy, such as auranofin ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT03456700

Auranofin and Sirolimus in Treating Participants With ... 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 ...