Olaparib + Chemotherapy for Prostate Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled infection, Viral hepatitis, Leukemia, 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: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug olaparib (Lynparza), administered after a specific chemotherapy combination, can help manage aggressive variant prostate cancer (AVPC). The study will also assess the safety of these drugs when used together. Participants will receive cabazitaxel (Jevtana) and carboplatin (Paraplatin or Carboplatinum), followed by olaparib, or they might be placed in an observation group. Men with aggressive prostate cancer that has spread to other parts of the body and meet specific disease criteria may be eligible to join. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that interact with olaparib, such as strong or moderate CYP3A4 inhibitors and inducers. If you are on these, a washout period (time without taking these medications) of 3 to 5 weeks is required before starting the trial.

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

Research has shown that the combination of cabazitaxel and carboplatin is safe and generally well-tolerated. Some studies found that while this combination can cause more side effects, most patients manage them. The most common side effects include low blood counts, fatigue, and nausea.

Olaparib is already approved for treating other cancers, such as ovarian cancer, and is also used for prostate cancer in some cases. Common side effects include low red blood cells (anemia), nausea, fatigue, and reduced appetite. These effects are usually mild and manageable.

Overall, both treatments have a history of being safe for most people. However, like any treatment, they can have side effects. Concerns should be discussed with the study doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine traditional chemotherapy with a cutting-edge drug, Olaparib. Olaparib is a PARP inhibitor, which means it targets and blocks a protein that cancer cells need to repair their DNA, potentially making the cancer more vulnerable to treatment. This is different from standard prostate cancer treatments, which typically focus on hormonal therapies or chemotherapy alone. By adding Olaparib to the mix, researchers hope to enhance the effectiveness of chemotherapy, offering a new approach that could improve outcomes for patients with advanced prostate cancer.

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

Research has shown that using cabazitaxel with carboplatin, which participants in this trial may receive, might be more effective than cabazitaxel alone for treating aggressive prostate cancer. Studies have found that adding carboplatin can benefit patients who do not respond well to cabazitaxel alone.

Additionally, olaparib, another treatment option in this trial, has shown potential in extending the lives of patients with advanced prostate cancer. Specifically, some studies demonstrated that patients taking olaparib had better outcomes and lived longer than those on other treatments. These findings suggest that the treatment combinations tested in this trial could effectively manage aggressive prostate cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Ana M. Aparicio, MD

Principal Investigator

UT MD Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for men over 18 with aggressive variant prostate cancer (AVPC) that's resistant to castration and has spread. They must have normal organ function, be able to swallow pills, consent to genetic research, and use birth control if needed. Excluded are those with certain medical conditions or who've had specific treatments for CRPC.

Inclusion Criteria

I am a man aged 18 or older.

My prostate cancer diagnosis was confirmed through lab tests.

I can perform daily activities with minimal assistance.

Exclusion Criteria

I have been treated for prostate cancer with specific drugs.

I am allergic to olaparib, carboplatin, or cabazitaxel.

Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive cabazitaxel and carboplatin intravenously on Day 1 of Cycles 1-6, and prednisone by mouth twice daily on Days 1-21 of Cycles 1-6

18 weeks

6 visits (in-person)

Maintenance Treatment

Participants in Group 1 receive olaparib by mouth twice daily starting on Day 1 of Cycle 7

As long as beneficial

Every 3 cycles after Cycle 10

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to one year from randomization

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cabazitaxel
• Carboplatin
• Olaparib
• Prednisone 5Mg

Trial Overview The study tests if olaparib can control AVPC after treatment with cabazitaxel, carboplatin, and prednisone. It's an investigational study of these drugs' combination; up to 96 participants at MD Anderson will receive this regimen following informed consent.

How Is the Trial Designed?

Group I: Olaparib Maintenance Experimental Treatment 1 Intervention

Participants randomized to receive Olaparib by mouth twice daily on Day 1 of cycle 7.

Group II: Cabazitaxel + Carboplatin Experimental Treatment 3 Interventions

Cabazitaxel, Cabazitaxel and Carboplatin intravenously on day 1 of cycles 1-6. Prednisone by mouth twice daily on days 1-21 of cycles 1-6.

Group III: Observation Only Active Control 1 Intervention

Participants randomized to observation only beginning cycle 7.

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+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

BRCA1 and BRCA2 mutations significantly increase the risk and aggressiveness of prostate cancer, highlighting the importance of genetic testing in prostate oncology.

Olaparib, an oral PARP inhibitor, has shown efficacy and good tolerance in phase II trials for patients with advanced castration-resistant prostate cancer, making it a promising treatment option while awaiting further phase III trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defective DNA repair mechanisms in prostate cancer: impact of olaparib. De Felice, F., Tombolini, V., Marampon, F., et al.[2018]

In a study involving 77 patients with metastatic or recurrent women's cancer, the combination of olaparib and carboplatin was found to be safe and effective, with a response rate of 46%, particularly higher in BRCA mutation carriers (68% vs. 19%).

The sequence of drug administration matters: giving carboplatin before olaparib increased olaparib clearance and reduced its bioavailability, suggesting that carboplatin should be administered first to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer. Lee, JM., Peer, CJ., Yu, M., et al.[2019]

The combination of olaparib and abiraterone significantly improves radiographic progression-free survival and other key progression metrics in patients with metastatic castration-resistant prostate cancer, based on a meta-analysis of two randomized controlled trials involving 938 patients.

While the combination therapy shows efficacy, it is associated with a higher risk of high-grade anemia compared to monotherapy, indicating a need for careful management of treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized controlled trials. Luo, Z., Zhu, B., Xu, H., et al.[2023]

Cabazitaxel is an effective second-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC), showing a median survival of 15.1 months compared to 12.7 months with mitoxantrone in a randomized trial.

While cabazitaxel has demonstrated efficacy, it is associated with significant adverse effects, including myelosuppression and febrile neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. Nightingale, G., Ryu, J.[2023]

In a phase 2 trial involving 142 patients with metastatic castration-resistant prostate cancer, the combination of olaparib and abiraterone significantly improved radiographic progression-free survival (rPFS) to a median of 13.8 months compared to 8.2 months with placebo and abiraterone, indicating enhanced efficacy of the treatment.

While the combination treatment showed clinical benefits, it also resulted in a higher incidence of serious adverse events, including a treatment-related death, suggesting that while effective, the combination may carry increased risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Clarke, N., Wiechno, P., Alekseev, B., et al.[2019]

The combination of olaparib and carboplatin was found to be safe and effective in treating breast and ovarian cancer in patients with germline BRCA1 or BRCA2 mutations, with 50% of patients showing a partial response and one patient achieving a complete response.

Proteomic analysis indicated that high levels of FOXO3a expression before treatment may predict a better response to the therapy, suggesting a potential biomarker for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. Lee, JM., Hays, JL., Annunziata, CM., et al.[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]

Cabazitaxel, when combined with prednisone, significantly improves overall survival in patients with hormone-refractory metastatic prostate cancer who have previously been treated with docetaxel, as shown in the pivotal TROPIC trial.

The treatment also enhances progression-free survival and response rates for tumor and PSA levels, while maintaining an acceptable safety profile, with common side effects including hematological issues and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer. Keating, GM.[2021]

Cabazitaxel, a new chemotherapy drug, has been shown to improve overall survival by 2.4 months in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment, compared to the older drug mitoxantrone.

While cabazitaxel is effective, it carries a risk of significant hematologic toxicity, including febrile neutropenia, necessitating the use of hematopoietic growth factors in cases of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer]. Lheureux, S., Joly, F.[2018]

Citations

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A Phase III Study of Cabazitaxel With or Without ... This phase III trial compares the effect of adding carboplatin to the standard of care chemotherapy drug cabazitaxel versus cabazitaxel alone in treating ...

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Combining Cabazitaxel and Carboplatin to Treat Castrate- ... Previous studies showed that treatment with cabazitaxel and carboplatin may work better than cabazitaxel in patients with AVPC. This trial will ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e17052

Real world outcomes with cabazitaxel (cab) plus ... This is the first study showing that the addition of car in those not responding to cab can recapture PSA response in roughly one third of patients.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31515154/

Cabazitaxel plus carboplatin for the treatment of ... - PubMed Carboplatin added to cabazitaxel showed improved clinical efficacy compared with cabazitaxel alone for men with metastatic castration-resistant prostate cancer.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1558767323002823

Combined Cabazitaxel and Carboplatin Treatment of ... In this study we showed that patients with PSA progression during cabazitaxel monotherapy could benefit from the addition of carboplatin to cabazitaxel.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6858999/

Cabazitaxel plus carboplatin for the treatment of men with ... Although adverse events were more common with the combination, the treatment was safe and generally well tolerated. Our data suggest that taxane ...

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30408-5/abstract

Cabazitaxel plus carboplatin for the treatment of men with ... Carboplatin added to cabazitaxel showed improved clinical efficacy compared with cabazitaxel alone for men with metastatic castration-resistant ...

8. targetedonc.com targetedonc.com/view/addition-of-carboplatin-to-cabazitaxel-promising-for-mcrpc-

Addition of Carboplatin to Cabazitaxel Promising for mCRPC Cabazitaxel in combination with carboplatin demonstrated an improvement in progression-free survival in comparison with cabazitaxel alone in men ...