Combination Therapies for Metastatic Prostate Cancer

(KNIGHTS Trial)

Overseen By Phuoc Tran, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must not be taking: PARP inhibitors, Antiretrovirals

Disqualifiers: Castration-resistant prostate cancer, Uncontrolled hypertension, Active malignancies, 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: Unknown

Duration: 6 months

88 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, long-term use of systemically administered corticosteroids is not allowed, and certain medications that interfere with the study drugs may also be restricted. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of abiraterone acetate and prednisone for metastatic prostate cancer?

Research shows that abiraterone acetate combined with prednisone improves survival and quality of life for patients with metastatic prostate cancer, especially when added to standard androgen deprivation therapy (ADT). This combination has been effective in both hormone-sensitive and castration-resistant forms of the disease. ^{1 2 3 4 5}

Is the combination of abiraterone acetate and prednisone safe for treating prostate cancer?

The combination of abiraterone acetate and prednisone has been studied in several clinical trials for prostate cancer, showing it is generally safe for use in humans. These studies, including the LATITUDE trial, have reported on the safety of this treatment when added to androgen deprivation therapy (ADT) for various stages of prostate cancer. ^{2 4 6 7 8}

How is the drug combination of ADT and prednisone unique for treating metastatic prostate cancer?

The combination of androgen deprivation therapy (ADT) and prednisone is unique because it includes abiraterone acetate, an oral hormone therapy that significantly improves survival and quality of life for patients with metastatic prostate cancer, especially when the cancer becomes resistant to traditional hormone therapy. ^{1 3 4 6 7}

What is the purpose of this trial?

The purpose of this research study is to compare the effects, good and/or bad, of using the standard of care treatment, hormonal therapy + Stereotactic Ablative Radiation (SABR) to the metastatic lesions, compared to standard of care and addition of 6-months of niraparib/abiraterone acetate combination pills and prednisone for participants with recurrent metastatic prostate cancer.

Eligibility Criteria

This trial is for individuals with recurrent metastatic prostate cancer, specifically those who have a small number of secondary tumors (oligometastatic). Participants should be suitable for hormonal therapy and targeted radiation (SABR), but details on specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

Able to swallow the study medication tablets whole

Bone scan within 6 months of enrollment

PSA > 0.5 but <50 at enrollment

Exclusion Criteria

Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study medication

Participants who have had the following ≤28 days prior to randomization

I've had radiation on the same spot where my cancer is now, preventing more radiation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care treatment with hormonal therapy and Stereotactic Ablative Radiation (SABR) or standard of care plus 6-months of niraparib/abiraterone acetate and prednisone

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PSA evaluation and quality-of-life assessments

18 months

Long-term follow-up

Participants are monitored for progression-free survival and treatment-related adverse events

4 years

Treatment Details

Interventions

• Androgen deprivation therapy (ADT)
• Niraparib/Abiraterone Acetate
• Prednisone
• Stereotactic ablative radiation therapy (SABR)

Trial Overview The study compares standard treatment (hormonal therapy + SABR) to the same standard care plus a 6-month course of niraparib/abiraterone acetate pills and prednisone. The goal is to see if adding these medications improves outcomes.

Participant Groups

Group I: Androgen deprivation therapy + Stereotactic ablative radiation Active Control 2 Interventions

Group II: Androgen deprivation therapy + Stereotactic ablative radiation + niraparib/abiraterone acetate Active Control 3 Interventions

Androgen deprivation therapy (ADT) is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Japan as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Switzerland as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

Abiraterone acetate combined with prednisone significantly improves overall survival (34.7 months vs 30.3 months) and radiologic progression-free survival (16.5 months vs 8.3 months) in patients with metastatic castration-resistant prostate cancer compared to placebo.

The treatment is generally well-tolerated, with manageable side effects primarily related to mineral corticoid excess, and it also enhances the perceived quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] Juárez Soto, A., Caballero Cobos, R., Campanario Pérez, R., et al.[2018]

Adding abiraterone acetate plus prednisone/prednisolone (AAP) to androgen deprivation therapy (ADT) significantly reduces the risk of death in men with metastatic hormone-sensitive prostate cancer (mHSPC) by 38%, translating to a 14% absolute improvement in overall survival over three years, based on data from two major trials involving 82% of participants.

The addition of AAP also leads to a 55% reduction in the risk of clinical or radiological progression-free survival, with a 28% absolute improvement at three years, although there is an increased risk of certain grade III-IV toxicities, particularly cardiac and hepatic, without an increase in overall mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis. Rydzewska, LHM., Burdett, S., Vale, CL., et al.[2023]

Both docetaxel combined with androgen deprivation therapy (ADT) and abiraterone acetate with prednisone/prednisolone plus ADT have been shown to improve survival rates in patients with metastatic castration-naive prostate cancer.

The choice between these treatments should be personalized based on the individual characteristics of the patient, ensuring the best possible outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Castration-naive Metastatic Prostate Cancer. Hamilou, Z., Baciarello, G., Fizazi, K.[2019]

In a study involving 1974 men with high-risk non-metastatic prostate cancer, combination therapy with abiraterone acetate and prednisolone significantly improved metastasis-free survival compared to androgen-deprivation therapy (ADT) alone, with a hazard ratio of 0.53, indicating a 47% reduction in the risk of metastasis.

The combination therapy also showed significant improvements in overall survival, prostate cancer-specific survival, and biochemical failure-free survival, although it was associated with a higher incidence of grade 3 or higher adverse events, such as hypertension and liver enzyme elevation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a real-world study involving 1108 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate plus prednisone (AAP) was found to be effective as both first-line and second-line treatment, with median overall survival of 27.1 months for first-line and 23.4 months for second-line therapy.

The treatment was well tolerated across all patient subgroups, including those with cardiovascular comorbidities, and no unexpected adverse events were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry. Bjartell, A., Lumen, N., Maroto, P., et al.[2021]

In a systematic review of randomized controlled trials involving newly diagnosed patients with metastatic hormone-sensitive prostate cancer, the combination of abiraterone acetate (AA), prednisone (P), and androgen deprivation therapy (ADT) showed a 72% to 87% probability of improving overall survival compared to docetaxel (DOC) plus ADT.

The AA + P + ADT regimen not only reduced the risk of disease progression more effectively (with a 93%-97% probability) but also improved quality of life for patients, particularly noticeable within the first three months of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: A network meta-analysis. Feyerabend, S., Saad, F., Li, T., et al.[2019]

In a study of 68 patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with abiraterone acetate (AA) plus prednisone (P) alone showed a comparable rate of radiographic progression-free survival (rPFS) to those continuing androgen deprivation therapy (ADT) alongside AA + P, suggesting that ADT may not be necessary.

Both treatment groups experienced moderate to severe adverse events, with 72% in the ADT group and 85% in the AA + P only group, indicating that while AA + P is effective, it is also associated with significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LHRH sparing therapy in patients with chemotherapy-naïve, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial. Ohlmann, CH., Jäschke, M., Jaehnig, P., et al.[2023]

In the final analysis of the LATITUDE study involving 1199 men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer, the combination of abiraterone acetate plus prednisone with androgen deprivation therapy (ADT) significantly improved overall survival, with a median of 53.3 months compared to 36.5 months for the placebo group.

The treatment had a manageable safety profile, with common grade 3-4 adverse events including hypertension and hypokalaemia, indicating that while there are risks, the benefits of improved survival support the use of this combination therapy as a standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Fizazi, K., Tran, N., Fein, L., et al.[2020]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] [2018]

2. England pubmed.ncbi.nlm.nih.gov

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of Castration-naive Metastatic Prostate Cancer. [2019]

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

Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. [2023]

5. France pubmed.ncbi.nlm.nih.gov

Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: A network meta-analysis. [2019]

7. England pubmed.ncbi.nlm.nih.gov

LHRH sparing therapy in patients with chemotherapy-naïve, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial. [2023]

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

Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. [2020]