Chemotherapy + PARP Inhibitor/Immunotherapy for Prostate Cancer

Overseen By Ana Aparicio

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Anti-PD1, Anti-PDL1

Disqualifiers: MDS/AML, Uncontrolled infection, Autoimmune disorders, 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: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy, a PARP inhibitor, and immunotherapy to treat aggressive variant prostate cancer that has spread. Drugs like cabazitaxel and carboplatin attack cancer cells, while niraparib (a PARP inhibitor) prevents tumors from repairing themselves, and cetrelimab (an immunotherapy) helps the immune system target the cancer. The goal is to determine if this combination can better control the cancer's progression. Individuals with confirmed metastatic prostate cancer who meet certain conditions, such as having specific types of metastases or genetic mutations, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients should not have unresolved side effects from previous cancer treatments and should not be on certain immunosuppressive medications. It's best to discuss your specific medications with the trial team.

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

Research has shown that niraparib is generally well-tolerated. Studies have found it can cause side effects such as anemia (low red blood cell count) and neutropenia (low white blood cell count), which can be managed with regular check-ups and treatment adjustments. The FDA has approved niraparib for other types of prostate cancer, suggesting it is relatively safe.

Early studies indicate that cetrelimab is safe when used with other treatments. As a monoclonal antibody, it helps the immune system fight cancer cells. Some early studies report it is well-tolerated, with no new safety concerns.

Both niraparib and cetrelimab have safety profiles that doctors can manage, meaning they have ways to handle any side effects that might occur during treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they combine chemotherapy with innovative agents like PARP inhibitors and immunotherapy. Unlike standard treatments, which often focus on hormone therapy, these regimens use niraparib, a PARP inhibitor, to target cancer cells' DNA repair mechanisms, potentially enhancing their vulnerability to treatment. Additionally, cetrelimab, an immunotherapy agent, helps the body’s immune system better recognize and attack cancer cells. This combination aims to not only stop tumor growth but also boost the body's natural defenses, offering a promising new angle in prostate cancer treatment.

What evidence suggests that this trial's treatments could be effective for aggressive variant prostate cancer?

Research has shown that niraparib, which participants in this trial may receive, holds promise for treating certain prostate cancers, particularly those with DNA repair issues. Studies have found that it can significantly slow cancer growth and reduce the risk of spreading. Cetrelimab, another treatment option in this trial, is a type of immunotherapy that has also demonstrated positive results. It enhances the body's immune response against prostate cancer, improving patient outcomes. Together, these treatments, used in different arms of this trial, attack cancer cells in various ways, potentially offering a more effective approach to managing aggressive prostate cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Ana Aparicio

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for men with aggressive variant metastatic prostate cancer who can swallow pills, have documented disease progression, and are willing to undergo treatment and follow-up. They must not have used immunosuppressive medication recently or had more than one chemotherapy line. Participants need functioning major organs and controlled infections, without certain medical conditions like uncontrolled heart issues or autoimmune disorders.

Inclusion Criteria

I am willing and able to follow the study's requirements, including treatments and visits.

Patients must consent to the MD Anderson Immunotherapy Platform laboratory protocol PA13-0291

My prostate cancer diagnosis was confirmed through lab tests.

Exclusion Criteria

I don't have major side effects from past cancer treatments that haven't gone away.

I have recovered from side effects of cancer treatment, except for specific prostate cancer therapies.

I have or had myelodysplastic syndrome or acute myeloid leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive cabazitaxel and carboplatin intravenously, with cetrelimab starting from cycle 2, repeated for up to 6 cycles

18 weeks

6 visits (in-person)

Maintenance

Patients receive niraparib orally daily, with or without cetrelimab intravenously, repeated every 28 days

Ongoing until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 to 90 days after last dose, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cabazitaxel
• Carboplatin
• Cetrelimab
• Niraparib

Trial Overview The study tests cabazitaxel, carboplatin, and cetrelimab followed by niraparib with or without cetrelimab. It aims to see if this combination can control the spread of aggressive prostate cancer by damaging tumor cells' DNA repair mechanisms and boosting the immune system's ability to fight cancer.

How Is the Trial Designed?

Group I: Group II (cetrelimab, niraparib) Experimental Treatment 4 Interventions

INDUCTION: Patients receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive cetrelimab IV over 30 minutes on day 1 and niraparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Group I (niraparib) Experimental Treatment 4 Interventions

INDUCTION: Patients receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive niraparib orally PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabazitaxel is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jevtana for:

• Hormone refractory metastatic prostate cancer

Approved in United States as Jevtana for:

• Metastatic castration-resistant prostate cancer

Approved in Canada as Jevtana for:

• Hormone-refractory metastatic prostate cancer

Approved in Japan as Jevtana for:

• Prostate cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Janssen Pharmaceutica

Industry Sponsor

Trials

43

Recruited

9,200+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Immunology Treatments

Top Products

Stelara (ustekinumab), Darzalex (daratumumab), Remicade (infliximab), Tremfya (guselkumab)

Published Research Related to This Trial

Cabazitaxel is a potentially effective treatment for castration-resistant prostate cancer (CRPC) in patients aged 80 years and older, showing similar efficacy in overall survival and PSA response rates compared to younger patients.

The safety profile of cabazitaxel is comparable across age groups, with high rates of adverse drug reactions (ADRs) in both patients aged <80 (77.2%) and ≥80 years (79.6%), primarily involving hematologic toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel in patients aged ≥80 years with castration-resistant prostate cancer: Results of a post-marketing surveillance study in Japan. Matsubara, N., Suzuki, K., Kazama, H., et al.[2021]

PARP inhibitors, specifically olaparib and rucaparib, have demonstrated effective antitumor activity and are FDA-approved for treating metastatic castrate-resistant prostate cancer with specific DNA repair defects.

Ongoing clinical trials for other PARP inhibitors like talazoparib, veliparib, and niraparib suggest that more treatment options may soon be available for patients with similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA Repair and Prostate Cancer: A Field Ripe for Harvest. Bryce, AH., Sartor, O., de Bono, J.[2021]

In a study involving 112 patients with metastatic castration-resistant prostate cancer (mCRPC), cabazitaxel treatment showed a low incidence of serious side effects, such as neutropenic sepsis (6.3%) and severe diarrhea (4.5%), indicating a favorable safety profile.

Patients reported trends towards improved quality of life during treatment, suggesting that cabazitaxel may enhance overall well-being for those whose cancer progressed after docetaxel, although careful patient selection is necessary due to potential toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final quality of life and safety data for patients with metastatic castration-resistant prostate cancer treated with cabazitaxel in the UK Early Access Programme (EAP) (NCT01254279). Bahl, A., Masson, S., Malik, Z., et al.[2022]

The combination of niraparib, a PARP inhibitor, with Radium-223 was found to be safe for treating metastatic castrate-resistant prostate cancer (mCRPC) in men without known BRCA mutations, with manageable dose-limiting toxicities (DLTs) primarily related to blood cell counts.

In a study of 30 patients, the maximum tolerated dose (MTD) varied based on prior chemotherapy exposure, indicating that personalized dosing may be necessary; further research is needed to explore biomarkers that could predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. Quinn, Z., Leiby, B., Sonpavde, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03551782

NCT03551782 | A Study of Cetrelimab (JNJ-63723283), a ... The primary hypothesis is that treatment with cetrelimab and apalutamide is safe and leads to improvement in the 12-week PSA response rate.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03551782

NCT03551782 | A Study of Cetrelimab (JNJ-63723283), ... The primary hypothesis is that treatment with cetrelimab and apalutamide is safe and leads to improvement in the 12-week PSA response rate.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8956549/

First-in-human, open-label, phase 1/2 study of the monoclonal ... In summary, the phase 1/2 LUC1001 study characterized the safety, pharmacokinetics, pharmacodynamics, and efficacy data of cetrelimab in ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.8_suppl.31

Anti-PD-1 antibody cetrelimab (JNJ-63723283) in patients ... 1. Results: As of 3 Sep 2018, 192 pts have been treated with cetrelimab from 80–800 mg Q2W and 480 mg Q4W. Median age was 60 ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03551782/

Clinical Trial: NCT03551782 The primary hypothesis is that treatment with cetrelimab and apalutamide is safe and leads to improvement in the 12-week PSA response rate.

6. xoma.com xoma.com/royaltyportfolio/jnj-63723283/

Cetrelimab (JNJ-63723283) - Clinical Trials A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Participants ...