Senaparib + Temozolomide for Ovarian Cancer

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

Trial Summary

What is the purpose of this trial?

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 clear cell or endometrioid ovarian cancers that have ARID1A pathologic variants.

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.

What data supports the effectiveness of the drug 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 patients with ovarian cancer, especially those with BRCA mutations. Olaparib has been used successfully as a maintenance therapy, extending overall survival in patients with platinum-sensitive relapsed ovarian cancer. ^{1 2 3 4 5}

How is the drug combination of Senaparib and Temozolomide unique for treating ovarian cancer?

Senaparib combined with Temozolomide is unique because it explores a novel combination of a PARP inhibitor (Senaparib) with a chemotherapy agent (Temozolomide), potentially offering a new approach for ovarian cancer treatment compared to existing therapies like olaparib, which is often used alone or with other drugs like bevacizumab. ^{1 6 7 8 9}

Research Team

Stephanie Gaillard, MD PhD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

References

1. 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]

2. England 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. [2023]

3. United States 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. [2023]

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

Olaparib Makes OS Gains in Ovarian Cancer. [2021]

5. United States 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. [2022]

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

Real-world clinical outcomes of olaparib therapy in Chinese patients with advanced serous ovarian cancer treated in Macau. [2021]

7. France pubmed.ncbi.nlm.nih.gov

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

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

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

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