Senaparib + Temozolomide for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Sidney Kimmel Cancer Center Clinical Research Office

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: PARP inhibitors, Temozolomide

Disqualifiers: HIV, Myeloid malignancies, Pregnancy, 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: 8

Duration: 28 days per cycle

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining Senaparib (a PARP inhibitor) and Temozolomide (an oral chemotherapy drug) against certain ovarian cancers, specifically clear cell or endometrioid types with specific ARID1A gene changes. The goal is to determine if these drugs can shrink tumors or slow their growth. Suitable participants have undergone at least two rounds of cancer treatment and have one of these specific ovarian cancer types. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that strong CYP3A4 inhibitors or inducers should not be used within 3 days of starting the study drugs. It's important to discuss your current medications with the study team to ensure there are no interactions.

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

A previous study found that the combination of Senaparib and Temozolomide was well-tolerated by some patients with advanced solid tumors, meaning many did not experience severe side effects. Other research has shown that Senaparib can significantly extend the period during which the tumor does not grow compared to a placebo, indicating its potential effectiveness. When tested together, Senaparib and Temozolomide demonstrated strong effects against tumor cells. These findings suggest that the combination is generally safe for humans, though individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Senaparib and Temozolomide for ovarian cancer because it offers a new approach compared to existing treatments like platinum-based chemotherapy. Unlike standard therapies, Senaparib is a PARP inhibitor that targets cancer cells by preventing them from repairing their DNA, which may lead to their death. Temozolomide, an oral chemotherapy drug, works to damage the DNA of cancer cells, enhancing the effects of Senaparib. This combination could potentially be more effective in tackling ovarian cancer by utilizing a dual mechanism to attack cancer cells from different angles.

What evidence suggests that the combination of Senaparib and Temozolomide could be effective for ovarian cancer?

Research shows that combining Senaparib and Temozolomide, which participants in this trial will receive, may help treat certain ovarian cancers. Early studies suggest this combination could be more effective at killing tumor cells, especially in patients whose cancer has specific genetic changes, such as the ARID1A mutation. Senaparib has demonstrated strong anti-tumor effects in some patients with advanced solid tumors and is generally well-tolerated. Although direct data for ovarian cancer is limited, similar drugs to Senaparib have improved survival rates in related conditions. These findings offer hope for those considering this treatment. ^{1 3 4 6 7}

Who Is on the Research Team?

Stephanie Gaillard, MD PhD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for patients with recurrent or persistent clear cell or endometrioid ovarian, fallopian tube, or primary peritoneal carcinoma who have an ARID1A mutation. They must have tried at least two cancer treatments before, or have a type of cancer that's resistant to platinum-based therapy. Participants need measurable disease and can't have had more than three prior cytotoxic therapies.

Inclusion Criteria

I can understand and am willing to sign the consent form, or I have someone who can legally do it for me.

My cancer has an ARID1A mutation found by advanced testing.

My test shows a specific genetic change in the ARID1A gene.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Senaparib 80mg orally daily Days 1-28 and Temozolomide 20mg daily Days 1-21 of a 28 day cycle

28 days per cycle

Tumor assessments every 8 weeks for first 3 cycles, then every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Senaparib
• Temozolomide

Trial Overview The study is testing the combination of Senaparib and Temozolomide in treating ovarian cancers with specific genetic changes (ARID1A mutations). It's a phase 2 trial aiming to see how well these drugs work together against the tumor.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Senaparib 80mg Temozolomide 20mg

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Impact Therapeutics

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

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 65 patients with advanced serous ovarian cancer in mainland China, olaparib showed a median progression-free survival (PFS) of 4.2 months, with better outcomes for patients with BRCA mutations (5.3 months) compared to those with wild-type BRCA (3.1 months).

Patients receiving olaparib as maintenance therapy had significantly longer PFS (between 9.0 and 10.0 months) compared to those on active therapy (3.1 to 3.0 months), and the treatment was generally well-tolerated, with 87% of patients experiencing low-grade adverse events like fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau. Cao, Y., Chen, H., Huang, Y., et al.[2021]

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 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 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]

In a study involving patients with newly diagnosed advanced ovarian cancer, the combination of olaparib and bevacizumab significantly improved overall survival (OS) in patients with homologous recombination deficiency (HRD), showing a 5-year OS rate of 65.5% compared to 48.4% for those receiving placebo.

The safety profile of olaparib plus bevacizumab was favorable, with low and balanced incidences of serious conditions like myelodysplastic syndrome and acute myeloid leukemia between treatment groups, confirming its potential as a standard care option for HRD-positive ovarian cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ray-Coquard, I., Leary, A., Pignata, S., et al.[2023]

Olaparib is established as a standard maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer who have BRCA mutations.

In the phase III SOLO 2 trial, Olaparib significantly extended overall survival by more than a year compared to a placebo, demonstrating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib Makes OS Gains in Ovarian Cancer. [2021]

In a phase II study involving 272 patients with platinum-sensitive relapsed ovarian cancer, olaparib showed significant efficacy, with objective response rates of 69.3% in germline BRCA1/BRCA2-mutated patients and 64.0% in somatic BRCA1/BRCA2-mutated patients, indicating strong effectiveness in these groups.

Olaparib also demonstrated a favorable safety profile, with common side effects including nausea and fatigue, consistent with previous studies, while median progression-free survival was notably longer in BRCAm cohorts compared to HRD-negative cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis. Cadoo, K., Simpkins, F., Mathews, C., et al.[2023]

Olaparib significantly improves progression-free survival (PFS) in both older (≥65 years) and younger (<65 years) patients with BRCA1/2-mutated recurrent platinum-sensitive ovarian cancer, showing no significant difference in efficacy between the age groups.

While olaparib is generally well-tolerated across ages, older patients experienced higher rates of treatment discontinuation due to toxicity and a greater frequency of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS), indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study. Trillsch, F., Mahner, S., Ataseven, B., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06617923

NCT06617923 | Study of Senaparib in Combination With ... This is a phase 2 study to test the effectiveness (anti-tumor activity) of the combination of the study drugs, Senaparib and Temozolomide, in patients with ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01228

Senaparib in Combination with Temozolomide for the ... Giving senaparib in combination with temozolomide may kill more tumor cells in patients with recurrent or persistent ARID1A mutated ovarian, fallopian tube or ...

3. impacttherapeutics.com impacttherapeutics.com/en/new/160.html

IMPACT Announces Presentation of the Clinical Data for ... The study results presented at this meeting include the safety, tolerability and the preliminary efficacy of senaparib in combination with TMZ in patients with ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.3102

A study of senaparib in combination with temozolomide for ... Preliminary data demonstrate senaparib has significant anti-tumor activity with good tolerability in some patients with advanced solid tumors.

5. withpower.com withpower.com/trial/senaparib-temozolomide-for-ovarian-cancer-52412

Senaparib + Temozolomide for Ovarian Cancer While there is no direct data on Senaparib and Temozolomide for ovarian cancer, similar drugs like Olaparib have shown effectiveness in improving survival in ...

6. impacttherapeutics.com impacttherapeutics.com/en/new/181.html

The Phase 3 clinical trial data of Senaparib has been ... According to the study findings published in Nature Medicine, Senaparib demonstrated significant improvement in PFS compared to placebo (median ...

7. aacrjournals.org aacrjournals.org/mct/article/24/1/47/750655/The-Discovery-of-a-Potent-PARP1-Inhibitor

The Discovery of a Potent PARP1 Inhibitor Senaparib In combination studies, Senaparib used with temozolomide had shown strong synergistic cytotoxicity in both in vitro and in vivo experiments.