Cirtuvivint + Olaparib for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Evamaria Kent Bravo, MS

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment combination for ovarian cancer that has not responded well to typical platinum-based chemotherapy. It aims to assess the safety and tolerability of Cirtuvivint (an experimental treatment) and Olaparib (a targeted therapy known as a PARP inhibitor) when used together. Participants will assist researchers in determining the appropriate dose for this combination therapy. Women diagnosed with high-grade serous or endometrioid ovarian cancer who have experienced issues with platinum treatments may be suitable candidates for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment combination, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Olaparib has been extensively studied for treating ovarian cancer. It is generally safe, though some people may experience side effects such as nausea, tiredness, and low blood cell counts. These side effects are important to consider but are common with many cancer treatments.

Cirtuvivint remains in the early stages of human safety testing. This study aims to learn more about how people respond to it when combined with Olaparib. Due to its early phase, information is limited, so researchers closely monitor participants' reactions to this combination. The study will help determine the safest dose for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cirtuvivint and Olaparib for ovarian cancer because it represents a fresh approach to treatment. Unlike traditional chemotherapy or PARP inhibitors alone, this combo targets cancer cells more precisely by combining the DNA repair inhibition of Olaparib with the kinase inhibition properties of Cirtuvivint. Cirtuvivint stands out due to its ability to disrupt cancer cell growth at a molecular level. This dual-action strategy may enhance effectiveness and potentially improve outcomes for patients who have limited options with conventional treatments.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that olaparib, one of the treatments in this trial, helps patients with recurrent ovarian cancer live longer. In one study, 67% of patients who took olaparib were still alive, compared to 46.5% of those who received a placebo. The other treatment in this trial, cirtuvivint, damages the DNA of ovarian cancer cells, potentially stopping the cancer from growing. This trial will test two different dose regimens combining olaparib and cirtuvivint to boost their effectiveness. While research on the combination continues, each treatment alone shows promise in fighting ovarian cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Bradley Corr

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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

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

Patients deemed otherwise clinically unfit for clinical trial per investigators discretion

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06856499

Study Details | NCT06856499 | Cirtuvivint/Olaparib in ... The purpose of this study is to learn about the safety and tolerability of Cirtuvivint in combination with Olaparib in platinum resistant ovarian cancer.

2. withpower.com withpower.com/trial/cirtuvivint-olaparib-for-ovarian-cancer-0fea2

Cirtuvivint + Olaparib for Ovarian Cancer Olaparib significantly improves overall survival in patients with recurrent platinum-sensitive ovarian cancer, with a hazard ratio of 1.24 based on a meta- ...

3. reporter.nih.gov reporter.nih.gov/search/vrzVJFoQ506TsXofgWqoiQ/project-details/10852678

Project Details Additionally, we demonstrate that cirtuvivint induces DNA damage and R-Loop formation in ovarian cancer cell lines. R-Loops are the DNA-RNA hybrids created in ...

4. onclive.com onclive.com/view/dr-elias-on-efficacy-data-with-olaparib-in-brca-mutated-ovarian-cancer

Dr Elias on Efficacy Data With Olaparib in BRCA-Mutated ... Elias highlighted that at the time of analysis, 67.0% of patients treated with olaparib vs 46.5% of patients treated with a placebo were alive.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09126

Cirtuvivint and Olaparib for the Treatment of Patients with ... This phase I trial tests the safety, side effects, and best dose of cirtuvivint when given with olaparib for the treatment of patients with ovarian cancer.

6. clin.larvol.com clin.larvol.com/trial-detail/NCT06856499

Cirtuvivint/Olaparib in Breast Cancer Susceptibility Gene/ ... To determine the safety and tolerability of combination Cirtuvivint and Olaparib in BRCA/HRD platinum resistant ovarian cancer as evaluated by CTCAE v5.0 ...

7. onclive.com onclive.com/view/olaparib-withstands-the-test-of-time-with-long-term-data-supporting-its-role-in-ovarian-cancer-treatment

Olaparib Withstands the Test of Time With Long-Term Data ... The long-term survival data from SOLO-1 showed that, at 7 years from randomization, the risk of death [was reduced by 45%] for those receiving ...