Cirtuvivint + Olaparib for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Samantha Hopp

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Must be taking: Cirtuvivint, Olaparib

Must not be taking: Systemic chemotherapy, Radiotherapy

Disqualifiers: Cardiac disease, Stroke, Leukemia, others

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

Compensation: Varies

Number of Visits: 28

Duration: 6 months

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn about the safety and tolerability of Cirtuvivint in combination with Olaparib in platinum resistant ovarian cancer. The study also aims to determine the recommended dose of the combination therapy. If a participant is a good fit for the study, and they enroll in the study, they will: * Visit the clinic often at the beginning of the study for physical exams, blood draws, vital signs, and other study and routine care procedures. After the first two months participants will visit the clinic every 28 days. * Take the study medications, Cirtuvivint and Olaparib. Participants will take Olaparib every day. Participants will either take Cirtuvivint 5 days per week or 2 days per week.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug combination Cirtuvivint and Olaparib for ovarian cancer?

Research shows that Olaparib alone or in combination with other drugs can effectively control ovarian cancer, especially in patients who are sensitive to platinum-based treatments. Olaparib has been shown to prolong the time patients live without the disease getting worse. ^{1 2 3 4 5}

Is the combination of Cirtuvivint and Olaparib safe for humans?

Olaparib has been studied extensively for ovarian cancer, showing it is generally safe, but it can cause side effects like nausea, fatigue, and low blood cell counts. There is no specific safety data available for Cirtuvivint in combination with Olaparib. ^{1 2 6 7 8}

How is the drug combination of Cirtuvivint and Olaparib unique for treating ovarian cancer?

The combination of Cirtuvivint and Olaparib is unique because it pairs a novel drug, Cirtuvivint, with Olaparib, a PARP inhibitor that targets cancer cells with specific genetic mutations (like BRCA mutations). This combination may offer a new approach by potentially enhancing the effectiveness of Olaparib in treating ovarian cancer, especially in patients with certain genetic profiles. ^{2 9 10 11 12}

Research Team

Bradley Corr

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for individuals with ovarian cancer, including fallopian tube and peritoneal cancers, that are resistant to platinum-based chemotherapy. Participants must have a gene defect related to breast cancer (BRCA) or a similar repair deficiency. They should be able to attend frequent clinic visits.

Inclusion Criteria

Provision to sign and date the consent form

I am a woman aged 18 or older.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have lasting side effects from cancer treatment, but not hair loss or numbness.

Patients deemed otherwise clinically unfit for clinical trial per investigators discretion

Prior known hypersensitivity reaction to study drugs and/or any of their excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cirtuvivint and Olaparib. Cirtuvivint is taken either 5 days on/2 days off or 2 days on/5 days off, while Olaparib is taken daily.

6 months

Frequent visits initially, then every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cirtuvivint
• Olaparib

Trial Overview The study tests the safety and best dose of Cirtuvivint combined with Olaparib in treating platinum-resistant ovarian cancer. Patients will take Olaparib daily and Cirtuvivint either five days or two days weekly, with regular clinic visits for monitoring.

Participant Groups

Group I: Dose Regimen 2 Experimental Treatment 2 Interventions

Patients on Dose Regimen 2 will take 300 mg PO BID olaparib in combination with 120 mg PO cirtuvivint for 2 days on and 5 days off

Group II: Dose Regimen 1 Experimental Treatment 2 Interventions

Patients on Dose Regimen 1 will take 300mg PO BID olaparib in combination with 80mg PO cirtuvivint for 5 days on and 2 days off.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Olaparib significantly improves overall survival in patients with recurrent platinum-sensitive ovarian cancer, with a hazard ratio of 1.24 based on a meta-analysis of 7 randomized controlled trials involving 2406 patients.

However, the treatment is associated with a higher incidence of adverse events, particularly for grades 3 or higher, indicating that while olaparib is effective, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. Chen, Q., Li, X., Zhang, Z., et al.[2022]

Olaparib (OLA) monotherapy showed a similar overall objective response rate (ORR) compared to chemotherapy (CT) in patients with relapsed ovarian cancer, with ORR of 24.3% for OLA and 28.3% for CT, indicating comparable efficacy.

In patients with platinum-resistant ovarian cancer (PROC) who had received more than four prior lines of treatment, OLA demonstrated a higher ORR of 22.9% compared to 0% for CT, suggesting that OLA may be more effective in heavily pretreated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. Vanderstichele, A., Loverix, L., Busschaert, P., et al.[2022]

In a study of 120 ovarian cancer patients, the combination of olaparib with paclitaxel and carboplatin significantly improved the objective remission rate and disease control rate compared to the standard treatment with paclitaxel and carboplatin alone.

The addition of olaparib also resulted in lower levels of tumor markers and a reduced rate of tumor metastasis after one year, all without increasing the incidence of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and paclitaxel in combination with carboplatin in treatment of ovarian cancer: influence on disease control. Zhang, H., Zhang, Y.[2022]

Olaparib-resistant ovarian cancer cells showed higher proliferation rates and increased expression of P38 and JNK proteins, indicating these pathways are involved in resistance mechanisms.

Combining P38 and JUN inhibitors significantly reduced cell growth and migration in resistant ovarian cancer cells, demonstrating potential as a therapeutic strategy to overcome olaparib resistance, with confirmed anti-tumor effects in mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell. Chen, X., Chen, Y., Lin, X., et al.[2018]

Olaparib is an effective oral treatment for advanced ovarian cancer in patients with BRCA1 or BRCA2 mutations, working by blocking DNA repair mechanisms in tumor cells, leading to selective cell death.

In clinical trials, olaparib significantly improved progression-free survival in patients with various types of ovarian cancer, and it is generally well tolerated, with mild side effects like nausea and fatigue being the most common.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of BRCA-mutated advanced ovarian cancer. Munroe, M., Kolesar, J.[2019]

In the phase III SOLO1 trial, maintenance treatment with olaparib significantly improved progression-free survival in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation, with 260 patients receiving olaparib compared to 131 on placebo.

The most common adverse events associated with olaparib, such as anemia and nausea, occurred early (within 3 months) but were manageable, with only a small number of patients needing to discontinue treatment, indicating a predictable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial. Colombo, N., Moore, K., Scambia, G., et al.[2022]

Olaparib is an effective first-line maintenance treatment for adults with advanced ovarian cancer who have responded to platinum-based chemotherapy, significantly improving progression-free survival compared to placebo in phase III trials.

When combined with bevacizumab, olaparib further enhances treatment efficacy in patients with homologous recombination deficiency (HRD), but does not show benefits in HRD-negative tumors, indicating its targeted effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. Paik, J.[2022]

Olaparib is an effective oral treatment for patients with BRCA mutation-positive ovarian cancer, approved for maintenance therapy after platinum-based chemotherapy, showing good tolerability with common side effects like nausea, fatigue, and anemia being mild to moderate.

Long-term monitoring is recommended due to a low risk of serious hematological complications, such as anemia and myelodysplastic syndrome, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. Lheureux, S., Bowering, V., Karakasis, K., et al.[2015]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Randomized CLIO/BGOG-ov10 trial of olaparib monotherapy versus physician's choice chemotherapy in relapsed ovarian cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Olaparib and paclitaxel in combination with carboplatin in treatment of ovarian cancer: influence on disease control. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Olaparib and advanced ovarian cancer: Summary of the past and looking into the future. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of BRCA-mutated advanced ovarian cancer. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

First-Line Treatment with Olaparib for Early Stage BRCA-Positive Ovarian Cancer: May It Be Possible? Hypothesis Potentially Generating a Line of Research. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of olaparib for treating ovarian cancer. [2015]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Emerging treatment options for recurrent ovarian cancer: the potential role of olaparib. [2021]