Combination Therapies for Metastatic Prostate Cancer

(KNIGHTS Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

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.

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Maryland Greenebaum Cancer Center Baltimore, MD

Who Is Running the Clinical Trial?

University of Maryland, Baltimore Lead Sponsor

Janssen Scientific Affairs, LLC Industry Sponsor

References

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

[Abiraterone in castration resistant prostate cancer.] [2018] Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease.

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] There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT.

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

Treatment of Castration-naive Metastatic Prostate Cancer. [2019] Both docetaxel+androgen deprivation therapy (ADT) and abiraterone acetate 1000mg/d+prednisone/prednisolone 5mg/d+ADT improved survival in patients with metastatic castration-naive prostate cancer. Their use should be offered and guided by patient's own characteristics.

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] Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population.

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] Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

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] Androgen deprivation therapy (ADT) has long been the gold standard for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical trials have demonstrated significant survival benefits when docetaxel (DOC) or abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating comparison of these combination treatments.

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] Although the benefit of androgen deprivation therapy (ADT) continuation in metastatic castration-resistant prostate cancer (mCRPC) remains controversial, clinical evidence is lacking. Recent results indicated that treatment with abiraterone acetate (AA) plus prednisone (P) further suppresses serum testosterone levels over ADT alone, suggesting that continuation of ADT in the treatment of mCRPC may not be necessary.

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] In the interim analyses of the LATITUDE study, the addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) led to a significant improvement in overall survival and radiographic progression-free survival compared with placebos plus ADT in men with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (mCSPC). Here, we present long-term survival outcomes and safety of abiraterone acetate plus prednisone and ADT from the final analysis of the LATITUDE study.