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

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well docetaxel with carboplatin followed by rucaparib camsylate works in treating patients with metastatic castration resistant prostate cancer (spread outside of prostate and resistant to testosterone suppression) with homologous recombination DNA repair deficiency. Chemotherapy drugs, such as docetaxel and carboplatin, work to stop the growth of cancer cells, by stopping them from dividing or spreading. Rucaparib camsylate may stop the growth of tumor cells with defects in the ability to repair mistakes in DNA by forcing additional errors so that the cancer cells cannot overcome the number of errors and will then die. Giving induction docetaxel and carboplatin followed by maintenance rucaparib camsylate may work better in treating patients with castration resistant prostate cancer.

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.

What data supports the effectiveness of the drug combination of chemotherapy and Rucaparib for prostate cancer?

Research shows that docetaxel, a component of the treatment, can extend survival in prostate cancer patients, and carboplatin may enhance its effectiveness when combined with taxanes like docetaxel. Additionally, early results with poly(ADP-ribose) polymerase inhibitors, like Rucaparib, show promise in certain prostate cancer patients. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs like carboplatin and docetaxel safe for prostate cancer treatment?

Research shows that combining docetaxel and carboplatin in treating prostate cancer has been studied for safety, with some reports of toxicity (side effects) in patients. These studies suggest that while the combination can be effective, it may also cause side effects, so monitoring by healthcare professionals is important. ^{2 6 7 8 9}

What makes the chemotherapy + rucaparib treatment for prostate cancer unique?

This treatment combines chemotherapy drugs carboplatin and docetaxel with rucaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, which may offer a novel approach by targeting specific molecular features of prostate cancer, especially in patients with certain genetic profiles. This combination could potentially enhance the effectiveness of treatment in cases where standard therapies have failed. ^{1 2 3 10 11}

Research Team

Heather H. Cheng

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

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

Management of Castration-Resistant, Taxane-Resistant Prostate Cancer. [2018]

2. England 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. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

[Second line therapy for castration-resistant prostate cancer (CRPC)]. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Docetaxel (taxotere) in the treatment of prostate cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. [2018]

7. China pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer]. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience. [2021]

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

Phase-II study of docetaxel, estramustine phosphate, and carboplatin in patients with hormone-refractory prostate cancer. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Response to docetaxel/carboplatin-based chemotherapy as first- and second-line therapy in patients with metastatic hormone-refractory prostate cancer. [2018]

11. United States 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. [2020]