Chemotherapy + Rucaparib for Prostate Cancer

Overseen By Heather H. Cheng

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: GnRH analogues

Must not be taking: PARP inhibitors

Disqualifiers: Other neoplastic disorders, CNS metastases, HIV, 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of chemotherapy drugs, docetaxel and carboplatin, followed by a maintenance drug called rucaparib camsylate (a type of targeted therapy), can effectively treat prostate cancer that has spread and resists testosterone-lowering treatments. The focus is on patients whose cancer has a specific weakness in repairing DNA damage. Men with prostate cancer that has resisted other treatments and has either spread to the bones or is visible on scans might be suitable candidates. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot have had certain treatments like a PARP inhibitor or platinum chemotherapy in the castration-resistant setting. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of docetaxel, carboplatin, and rucaparib is generally well-tolerated by prostate cancer patients. In one study, patients received docetaxel and carboplatin first, followed by rucaparib to maintain the treatment's effects. Most patients handled these treatments without major problems.

Common side effects included tiredness, nausea, and changes in blood cell levels. However, these were usually manageable and did not cause most patients to stop treatment.

Rucaparib is already approved for other uses, so its safety is well-known, providing reassurance about its use in this trial. Overall, the treatment has been found to be tolerable, with side effects that can often be managed. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about the combination of chemotherapy with rucaparib for treating prostate cancer because it introduces a targeted approach that differs from traditional treatments. Most standard therapies focus on hormone manipulation or conventional chemotherapy, but rucaparib is a PARP inhibitor, which specifically targets cancer cells by exploiting their DNA repair weaknesses. This targeted mechanism can potentially enhance the effectiveness of chemotherapy agents like carboplatin and docetaxel, possibly leading to better outcomes with fewer side effects. By combining these drugs, there's hope for improved patient responses and prolonged remission in prostate cancer patients.

What evidence suggests that this trial's treatments could be effective for metastatic castration resistant prostate cancer?

This trial will evaluate the effectiveness of using the drugs docetaxel and carboplatin, followed by rucaparib camsylate, for patients with a certain type of advanced prostate cancer. Docetaxel and carboplatin stop cancer cells from growing and spreading. Rucaparib camsylate is believed to cause extra mistakes in the DNA of cancer cells, which they can't repair, leading to their death. However, research has shown that this combination may not significantly help patients with specific DNA repair issues. While the treatment seems promising in theory, current evidence does not show significant improvement for all patients with these particular cancer traits. ^{1 2 6 7 8}

Who Is on the Research Team?

Heather H. Cheng

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Men with metastatic castration resistant prostate cancer and DNA repair deficiencies (like BRCA mutations) are eligible. They must be on hormone therapy, have no recent platinum chemotherapy or PARP inhibitors, and not suffer from severe heart disease or other conditions that could interfere with the trial.

Inclusion Criteria

My cancer has a specific genetic change related to DNA repair.

My liver enzymes are within the required limits for the study.

My kidney function, measured by creatinine or GFR, is within the required range.

Exclusion Criteria

Any condition(s), medical or otherwise, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained

I have serious heart issues, including a recent heart attack or severe heart disease.

I've had platinum-based chemotherapy for cancer that didn't respond to hormone therapy, but it's been over 6 months since my last dose.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive docetaxel and carboplatin intravenously on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

12 weeks

4 visits (in-person)

Maintenance

Patients receive rucaparib camsylate orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ongoing until disease progression

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Docetaxel
• Rucaparib Camsylate

Trial Overview The trial is testing a combination of chemotherapy drugs docetaxel and carboplatin followed by rucaparib camsylate maintenance therapy to see if it's effective for prostate cancer patients who can't fix DNA damage well.

How Is the Trial Designed?

Group I: Treatment (docetaxel, carboplatin, rucaparib camsylate) Experimental Treatment 5 Interventions

INDUCTION: Patients receive docetaxel IV and carboplatin IV on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive rucaparib camsylate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Published Research Related to This Trial

In a study of 310 patients with castration-resistant prostate cancer (CRPC), the combination of taxane-estramustine-carboplatin (TEC) chemotherapy resulted in a significant prostate-specific antigen (PSA) response rate of 69%.

The 12-month survival estimate for patients receiving TEC chemotherapy was 79%, which is notably higher than the median predicted survival of 59%, indicating that TEC may provide substantial clinical benefits in CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of carboplatin-taxane combinations in the management of castration-resistant prostate cancer: a pooled analysis of seven prospective clinical trials. Regan, MM., O'Donnell, EK., Kelly, WK., et al.[2021]

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

In a study of 47 men with metastatic castration-resistant prostate cancer (mCRPC), combining androgen deprivation therapy (ADT) with docetaxel chemotherapy (DTX) significantly improved radiographic progression-free survival (rPFS) compared to DTX alone, with median rPFS of 9.0 months versus 6.0 months.

While overall survival (OS) was similar between the two groups (42.0 months for DTX+ADT and 38.0 months for DTX), the study indicates that concurrent ADT with DTX is a beneficial strategy for improving disease control in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. Jang, HS., Koo, KC., Cho, KS., et al.[2018]

In a study of 15 patients with metastatic castration-resistant prostate cancer (mCRPC), docetaxel combined with carboplatin showed promising short-term efficacy, with 66.7% of patients experiencing a PSA decline of over 50%.

The treatment was generally well-tolerated, with most adverse reactions, such as bone marrow suppression and gastrointestinal issues, being manageable, indicating a favorable safety profile for this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer]. Bai, GC., Song, Y., Jin, J., et al.[2022]

Docetaxel shows a 42% response rate in treating androgen-independent prostate cancer based on four Phase II studies, indicating its significant efficacy as a single-agent therapy.

Combining docetaxel with estramustine may enhance response rates but also increases toxicity, and ongoing Phase III studies are expected to clarify the best use of docetaxel in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. Beer, TM., El-Geneidi, M., Eilers, KM.[2018]

Carboplatin and paclitaxel (CP) demonstrated moderate efficacy in treating castration-resistant prostate cancer (CRPC), particularly as a first-line treatment, with a 55.6% PSA response rate and a median overall survival of 19 months for patients receiving it first.

In contrast, CP showed limited effectiveness in the third-line setting, with only a 10% PSA response rate and a median overall survival of 6 months, suggesting it may be more beneficial for patients with specific genetic mutations, like BRCA2 defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer. Fujiwara, M., Akamatsu, S., Sumiyoshi, T., et al.[2020]

Docetaxel chemotherapy is a standard first-line treatment for castration-resistant prostate cancer, providing a modest overall survival benefit of 2 months, but patients typically progress to a docetaxel-insensitive phase within 6-9 months.

Emerging therapies like cabazitaxel, sipuleucel-T, and abiraterone show promise for secondary treatment options, highlighting the need for more clinical data to explore various combinations and sequences of therapies for better outcomes in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second line therapy for castration-resistant prostate cancer (CRPC)]. Molitor, B., Börgermann, C.[2021]

Citations

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Results from a Phase 2 Study of Induction Docetaxel and ... Induction platinum-based chemotherapy followed by maintenance PARPi therapy did not improve outcomes for patients with mCRPC broadly selected for HRR ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40413129/

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Docetaxel, Carboplatin, and Rucaparib Camsylate in ... This phase II trial studies how well docetaxel with carboplatin followed by rucaparib camsylate works in treating patients with metastatic castration ...

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PLATIPARP: A phase 2 study of induction docetaxel and ... We report results from a single-center phase 2 study investigating whether induction chemotherapy (IC) with docetaxel and carboplatin followed by maintenance ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT449686

PLATIPARP: A phase 2 study of induction docetaxel and ... Patients received IC with 4 cycles of docetaxel 60mg/m2 with carboplatin AUC 5 IV q21 days, followed by the PARPi rucaparib 600mg BID continuously as ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10796584/

Platinum-based chemotherapy in metastatic prostate cancer This review aims to explore the potential of platinum-based chemotherapy in the context of prostate cancer, and more in detail in homologous recombination ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S155876732400051X

Treatment Patterns and Clinical Outcomes Among Patients ... The current chart review study was conducted to describe the treatment patterns and clinical outcomes observed among patients with mCRPC harboring somatic HRR ...

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A review of treatments targeting DNA-repair gene defects ... Docetaxel, carboplatin, and rucaparib camsylate in treating patients with metastatic castration resistant prostate cancer with homologous ...