Rucaparib + Enzalutamide for Prostate Cancer

(CASPAR Trial)

Not currently recruiting at 447 trial locations

Overseen By Arpit Rao, MD

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Androgen deprivation

Must not be taking: CYP2C8 inhibitors, CYP3A4 inducers

Disqualifiers: CNS metastases, Seizure history, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for prostate cancer that has spread and does not respond to standard testosterone-blocking therapy. It compares the effectiveness of using two drugs together—enzalutamide (Xtandi), which blocks testosterone's effects, and rucaparib, which prevents cancer cells from repairing their DNA—to using enzalutamide alone. The researchers hope this combination will help patients live longer or slow cancer growth more effectively. Men with prostate cancer resistant to testosterone-deprivation therapy and showing signs of progression are suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are strong inhibitors of CYP2C8 or inducers of CYP3A4 enzymes before joining. You should also closely monitor any medications that are substrates of CYP3A4, CYP2C9, and CYP2C19 enzymes with your doctor.

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

Research has shown that using rucaparib and enzalutamide together is generally safe and may help treat prostate cancer. Early results suggest that most patients tolerate this combination well. However, it may cause more serious side effects than using enzalutamide alone. Studies indicate that the risk of serious side effects could be 10–30% higher with both drugs. While this might seem concerning, the two drugs do not interact in unexpected ways, indicating they work well together. Overall, the treatment appears safe, but participants should be aware of the possibility of increased side effects. ^{1 2 3 4 5}

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

Rucaparib + enzalutamide is unique because it combines two powerful mechanisms to tackle prostate cancer. While most treatments focus on hormone therapy to slow cancer growth, rucaparib introduces a new angle by targeting the DNA repair pathways in cancer cells, specifically inhibiting PARP enzymes. This means it's not just about cutting off the cancer's fuel, but also about exploiting its weaknesses in repairing itself. Researchers are excited because this dual approach might offer a more effective way to stop cancer progression compared to standard treatments like enzalutamide alone.

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

Research has shown that combining rucaparib and enzalutamide, which participants in one arm of this trial will receive, may effectively treat advanced prostate cancer that no longer responds to standard hormone therapy. This combination blocks the cancer's use of testosterone and interferes with its DNA repair, potentially slowing the cancer's growth. Earlier studies demonstrated that enzalutamide alone, which participants in another arm of this trial will receive, helped patients live longer without their cancer worsening. Adding rucaparib, which targets the cancer cells' DNA repair, could enhance the treatment's effectiveness. Overall, early results suggest this treatment might help patients live longer or slow the cancer's spread. ^{2 4 6 7 8}

Who Is on the Research Team?

Arpit Rao, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

Men with metastatic prostate cancer resistant to testosterone-deprivation therapy are eligible. They must have documented prostate adenocarcinoma, radiographic progression, and no central nervous system metastases that aren't stable or treated. Participants need to be off certain drugs affecting liver enzymes and recovered from major surgeries or treatments. No prior treatment for metastatic castration-resistant prostate cancer is allowed.

Inclusion Criteria

I have available tissue samples from my cancer for testing.

My cancer has spread and can be measured or not.

Total bilirubin =< 1.5 x upper limit of normal (ULN)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enzalutamide and rucaparib or enzalutamide and placebo, with androgen deprivation therapy if applicable. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months for 2 years, then every 6 months for 3 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Rucaparib camsylate

Trial Overview The trial tests if adding Rucaparib (a PARP inhibitor) to Enzalutamide improves outcomes in men whose prostate cancer has spread and resists hormone therapy. It's a phase III study where patients are randomly assigned either the combination of both drugs or Enzalutamide alone, plus placebos as needed.

How Is the Trial Designed?

Group I: Arm I (enzalutamide, rucaparib) Experimental Treatment 7 Interventions

Patients receive enzalutamide PO QD and rucaparib PO BID. Patients who did not undergo bilateral orchiectomy also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (enzalutamide, placebo) Active Control 6 Interventions

Patients receive enzalutamide PO QD and placebo PO BID. Patients who did not undergo bilateral orchiectomy also receive ADT consisting of leuprolide acetate IM, goserelin acetate SC every 12 weeks or degarelix SC. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer across various disease subgroups, including nonvisceral and visceral disease, as well as low- and high-volume bone disease.

The treatment was well tolerated, showing clinically significant benefits in overall survival (OS) for most subgroups, although the results were less definitive for patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer. Evans, CP., Higano, CS., Keane, T., et al.[2022]

In the SPARTAN study, apalutamide combined with androgen deprivation therapy (ADT) led to rapid and significant reductions in prostate-specific antigen (PSA) levels in most patients, with 90% achieving at least a 50% reduction by 6 months, compared to only 1.5% in the placebo group.

Deep PSA responses (≥90% reduction or PSA ≤0.2 ng/ml) at 6 months were strongly linked to improved outcomes, including metastasis-free survival and overall survival, indicating that early PSA monitoring can be a valuable prognostic tool for patients with high-risk nonmetastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. Saad, F., Small, EJ., Feng, FY., et al.[2022]

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

In men with metastatic hormone-sensitive prostate cancer, enzalutamide, when combined with androgen-deprivation therapy, significantly prolonged radiographic progression-free survival compared to a placebo.

This finding highlights the efficacy of enzalutamide as an androgen-receptor inhibitor in improving outcomes for patients undergoing treatment for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eyeing Enzalutamide for Hormone-Sensitive Prostate Cancer. [2020]

In a phase 2 study involving 60 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide treatment led to a significant decline in prostate-specific antigen (PSA) levels in 45% of patients, indicating its efficacy in managing this advanced cancer.

The study found that the presence of the androgen receptor variant ARV7 was linked to primary resistance to enzalutamide, suggesting that certain androgen signaling characteristics before treatment can predict patient response to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Efstathiou, E., Titus, M., Wen, S., et al.[2022]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

In a real-world study involving 1732 men with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide demonstrated a median time to treatment failure of 12.9 months for patients who had not previously received chemotherapy or abiraterone, compared to 8.4 months for those who had, indicating its efficacy in different treatment settings.

The safety profile of enzalutamide was consistent with previous clinical trials, with treatment-emergent adverse events reported in 51.0% of chemotherapy-naïve patients and 62.2% of post-chemotherapy patients, with fatigue being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE. Payne, H., Robinson, A., Rappe, B., et al.[2022]

In a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

Citations

1. urologytimes.com urologytimes.com/view/rucaparib-plus-enzalutamide-shows-early-promise-in-mcrpc

Rucaparib plus enzalutamide shows early promise in ... The combination of rucaparib (Rubraca) and enzalutamide (Xtandi) was shown to be safe with early signs of efficacy in patients with metastatic castration- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04455750

NCT04455750 | A Clinical Study Evaluating the Benefit of ... This randomized, placebo-controlled phase III trial is evaluating the benefit of rucaparib and enzalutamide combination therapy versus enzalutamide alone

3. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825000861

Empowering PARP inhibition through rational combination The advent of PARP inhibitors has substantially improved treatment outcomes across various cancer types. Among them, metastatic castration-resistant prostate ...

4. withpower.com withpower.com/trial/phase-3-prostatic-neoplasms-1-2021-33aa6

Rucaparib + Enzalutamide for Prostate Cancer (CASPAR ... Enzalutamide significantly improved radiographic progression-free survival (rPFS) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer ...

5. ascopubs.org ascopubs.org/doi/10.1200/OP-24-00690

Real-World Evidence of Combination Therapy Use in ... Real-world data from a large US administrative claims database were used to understand treatment patterns from 2017 to 2023 in individuals with ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.6_suppl.79

Rucaparib plus enzalutamide in patients (pts) with ... Conclusions: A combination of enzalutamide and rucaparib was not associated with a clinically significant effect on PK profiles of either drug.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214676

Rucaparib or Physician's Choice in Metastatic Prostate ... In the BRCA subgroup, 162 of 302 patients had died (data maturity, 54%); the median overall survival was 24.3 months (95% CI, 19.9 to 25.7) in ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S030438352300318X

an overview of PARP inhibitors for metastatic castration- ... The rate of grade ≥3 adverse events for the combination regimens is 10–30% higher when compared to an ARSI alone.