Niraparib + Copanlisib for Gynecologic Cancers

Overseen By Shannon Westin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Compensation: Varies

Number of Visits: 33

Duration: 28 days per cycle, repeated

31 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial studies the best dose and side effects of niraparib and copanlisib in treating patients with endometrial, ovarian, primary peritoneal, or fallopian tube cancer that has come back. Niraparib and copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use strong inhibitors or inducers of CYP3A4 from 14 days before the trial starts until the end of the study. If you are on systemic corticosteroids, the dose must be reduced to 15 mg of prednisone or equivalent 7 days before the trial.

What data supports the effectiveness of the drug combination of Niraparib and Copanlisib for gynecologic cancers?

Niraparib has been shown to improve progression-free survival in patients with advanced ovarian cancer, especially those who have responded to platinum-based chemotherapy. It is effective as a maintenance therapy, even in patients without specific genetic markers that typically predict better outcomes. ^{1 2 3 4 5}

Is the combination of Niraparib and Copanlisib safe for humans?

Niraparib has been studied for safety in various trials, showing that it can cause side effects like myelosuppression (a decrease in blood cell production) and thrombocytopenia (low platelet count), which were managed by adjusting the dose. There is no specific safety data available for the combination of Niraparib and Copanlisib. ^{1 2 3 6 7}

What makes the drug combination of Niraparib and Copanlisib unique for treating gynecologic cancers?

The combination of Niraparib and Copanlisib is unique because Niraparib is a PARP inhibitor that has shown effectiveness in prolonging progression-free survival in ovarian cancer patients, regardless of genetic mutations, while Copanlisib is a PI3K inhibitor, potentially offering a novel mechanism of action by targeting different pathways in cancer cells. ^{1 2 3 6 8}

Research Team

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with recurrent endometrial, ovarian, primary peritoneal, or fallopian tube cancer. Participants must have had any number of prior chemotherapies and a life expectancy of at least 3 months. They should be able to perform daily activities with little assistance (ECOG status 0-1), not be pregnant, use effective contraception, and meet certain health criteria.

Inclusion Criteria

Agreement to not donate blood during the study or for 90 days after the last dose of study treatment

You have not already tried too many different chemotherapy treatments for your recurrent endometrial or ovarian cancer.

You have a disease that can be measured or assessed using specific criteria.

Exclusion Criteria

You have recently used other treatments or medical procedures.

Certain medical conditions, infections, and immune system disorders.

Simultaneous enrollment in an interventional clinical trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib orally daily and copanlisib intravenously on specified days in 28-day cycles

28 days per cycle, repeated

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up at 30 and 90 days, then every 3 months

Treatment Details

Interventions

• Copanlisib
• Niraparib

Trial Overview The trial is testing the combination of two drugs: Niraparib and Copanlisib. It aims to find the best dose while observing side effects in patients whose cancer has returned. These drugs are believed to block enzymes that tumor cells need for growth.

Participant Groups

Group I: Treatment (niraparib, copanlisib) Experimental Treatment 2 Interventions

Patients receive niraparib PO daily on days 1-28 and copanlisib IV on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Niraparib significantly extends progression-free survival in patients with newly diagnosed advanced ovarian cancer, showing efficacy in both homologous-recombination deficiency positive (HRd) and negative (HRp) populations, based on a phase III trial.

The treatment has a manageable safety profile, with myelosuppression as the main concern, which can be effectively managed through monitoring and individualized dosing based on weight and platelet count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. Lee, A.[2022]

In a Phase 2 study involving 20 Japanese women with heavily pretreated ovarian cancer, niraparib demonstrated an objective response rate of 35%, indicating that it can effectively reduce tumor size in some patients.

The treatment was generally well-tolerated, with a high disease control rate of 90%, although common side effects included anemia and nausea, and 70% of patients experienced dose reductions or interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. Okamoto, A., Kondo, E., Nakamura, T., et al.[2021]

In a study of 105 patients with newly diagnosed advanced ovarian cancer, the combination of niraparib and bevacizumab as first-line maintenance therapy resulted in a promising progression-free survival (PFS) rate of 62% at 18 months, with even higher rates in patients with homologous recombination deficiency (76%).

The safety profile of this combination therapy was consistent with the known side effects of the individual drugs, with common treatment-related adverse events including thrombocytopenia, fatigue, and anemia, indicating that the treatment is manageable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. Hardesty, MM., Krivak, TC., Wright, GS., et al.[2022]

The combination treatment of dostarlimab and niraparib in patients with recurrent platinum-resistant ovarian cancer showed a low objective response rate of only 7.3%, leading to the early termination of the study due to insufficient efficacy.

Despite the treatment being generally safe with no new safety issues identified, 95.1% of patients experienced treatment-related adverse events, and health-related quality of life worsened over time, indicating a need for more effective therapies for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). Randall, LM., O'Malley, DM., Monk, BJ., et al.[2023]

Niraparib, a treatment for recurrent ovarian cancer, has a high dose reduction rate of 68.9% due to treatment-emergent adverse events, with thrombocytopenia being a notable cause for 3.3% of patients.

Baseline body weight and platelet count are significant predictors for the risk of severe thrombocytopenia, suggesting that patients with a body weight under 77 kg or platelet count below 150,000/µl may benefit from starting at a lower dose of 200 mg/day without compromising progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and dose modification for patients receiving niraparib. Berek, JS., Matulonis, UA., Peen, U., et al.[2021]

In the ENGOT-OV16/NOVA trial, patients aged 70 and older with recurrent ovarian cancer who received niraparib showed significant progression-free survival (PFS) benefits, with non-gBRCAmut patients achieving a median PFS of 11.3 months compared to 3.8 months for those on placebo.

The safety profile of niraparib in older patients was similar to that in younger patients, with common adverse events being hematologic issues like thrombocytopenia and anemia, suggesting that niraparib is a viable treatment option for older patients with recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial. Fabbro, M., Moore, KN., Dørum, A., et al.[2019]

Niraparib significantly improves progression-free survival and other key outcomes in patients with recurrent, platinum-sensitive ovarian cancer, based on the phase III NOVA trial involving a randomized, double-blind, placebo-controlled design.

The treatment has a manageable safety profile, with most serious side effects being blood-related issues, which can be effectively managed through dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. Heo, YA., Duggan, ST.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. [2019]

2. France pubmed.ncbi.nlm.nih.gov

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

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. [2021]

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

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. [2022]

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

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety and dose modification for patients receiving niraparib. [2021]

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

Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial. [2019]

8. France pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. [2019]