Standard Therapy + Surgery/Radiation for Prostate Cancer

Recruiting at329 trial locations

Overseen by Brian Chapin

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: SWOG Cancer Research Network

Must be taking: Standard systemic therapy

Must not be taking: Docetaxel

Disqualifiers: Brain metastases, Prior local therapy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have progressed while on standard systemic therapy, and you cannot plan to receive docetaxel after randomization.

What data supports the effectiveness of the drug abiraterone acetate in treating prostate cancer?

Research shows that abiraterone acetate, when used with prednisone, improves survival and quality of life in patients with metastatic castration-resistant prostate cancer. It also significantly prolongs overall survival compared to prednisone alone in patients who have failed docetaxel chemotherapy. ^{1 2 3 4 5}

Is the combination of standard therapy and surgery/radiation for prostate cancer generally safe for humans?

The combination of abiraterone and prednisone with standard therapy has been evaluated for safety in prostate cancer patients, showing it is generally safe, though specific side effects and patient conditions should be considered. Safety data from studies indicate that these treatments are well-tolerated, but individual responses can vary, and factors like patient health and potential side effects should be discussed with a healthcare provider. ^{1 6 7 8 9}

What makes this prostate cancer treatment unique?

This treatment is unique because it combines standard therapies like androgen deprivation therapy with additional drugs such as abiraterone and prednisone, which have shown to improve survival in prostate cancer patients. It also explores the use of surgery or radiation, offering a comprehensive approach that targets the cancer from multiple angles. ^{1 2 6 10 11}

Research Team

Brian Chapin

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

Men with metastatic prostate cancer who've had less than 28 weeks of standard therapy without disease progression are eligible. They must have a low testosterone level, no brain metastases, and an intact prostate with no prior local treatment for cancer. Prior treatments for benign conditions are okay. Participants should be able to complete quality-of-life assessments in English, Spanish or French.

Inclusion Criteria

My prostate is intact and I haven't had any treatment for prostate cancer.

STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone lab documented within 28 days prior to randomization. Any additional testosterone labs measured while receiving SST should be recorded as well as pretreatment initiation if available.

I have been on hormone therapy for prostate cancer for 22 to 28 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive one of six acceptable forms of standard systemic therapy (SST) for 22-28 weeks.

22-28 weeks

Regular visits for treatment administration

Randomization and Treatment

Participants are randomized to receive either continued SST or SST plus prostatectomy or radiation therapy.

4-8 weeks

Visits for surgery or radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

8 years

Treatment Details

Interventions

• Abiraterone (Hormone Therapy)
• Bicalutamide (Hormone Therapy)
• Degarelix (Hormone Therapy)
• Docetaxel (Chemotherapy)
• Flutamide (Hormone Therapy)
• Goserelin Acetate (Hormone Therapy)
• Histrelin Acetate (Hormone Therapy)
• Leuprolide Acetate (Hormone Therapy)
• Nilutamide (Hormone Therapy)
• Orchiectomy (Surgery)
• Prednisone (Hormone Therapy)
• Radiation Therapy (Radiation)
• Radical Prostatectomy (Surgery)
• Triptorelin (Hormone Therapy)

Trial Overview This phase III trial is testing if adding surgery (prostate removal) or radiation to the usual systemic therapy improves outcomes in men whose prostate cancer has spread. The study will compare the effects of these combined treatments on the growth and spread of cancer.

Participant Groups

Group I: Arm II (SST, prostatectomy or radiation therapy) Experimental Treatment 13 Interventions

Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone. Participants undergo prostatectomy within 8 weeks after randomization or radiation therapy within 4 weeks of randomization.

Group II: Arm I (SST) Active Control 11 Interventions

Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone.

Group III: Step 1 (pre-randomization) Active Control 13 Interventions

Standard treatment data collection prior to randomization

Abiraterone is already approved in Canada, Japan for the following indications:

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Dr. Charles D. Blanke

SWOG Cancer Research Network

Chief Executive Officer since 2012

MD from Oregon Health & Science University

Dr. Dawn Hershman

SWOG Cancer Research Network

Chief Medical Officer since 2020

MD from Columbia University

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

Dr. Lyudmila Bazhenova

Southwest Oncology Group

Chief Medical Officer since 2021

MD from University of California, San Diego

Dr. Richard Schilsky

Southwest Oncology Group

Chief Executive Officer since 2013

MD from University of California, San Diego

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a study involving 10 patients with castration-resistant prostate cancer, the combination of abiraterone acetate and triptorelin led to a significant decrease in PSA levels in 9 out of 10 patients, indicating effective treatment.

Additionally, two patients experienced regression of bone lesions, suggesting that this combination therapy may not only lower PSA levels but also positively impact bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Concomitant use of abiraterone acetate and triptorelin in patients with castration-resistant prostate cancer]. Rapoport, LM., Bezrukov, EA., Kondrashina, AV.[2018]

In a study involving 515 patients with hormone-sensitive prostate cancer, those receiving abiraterone acetate plus prednisone (AAP) alongside standard care reported a higher quality of life (QOL) compared to those receiving docetaxel plus standard care, with a mean difference of +3.9 points over two years.

The improvement in global-QOL scores for the AAP group was particularly significant during the first year, with increases of +5.7 points at one year and +8.3 points at two years, indicating that AAP may offer better patient-reported outcomes in terms of quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial. Rush, HL., Murphy, L., Morgans, AK., et al.[2023]

In a network meta-analysis of four trials involving treatments for castration-resistant, docetaxel-resistant metastatic prostate cancer, no significant differences in overall survival were found among abiraterone acetate, enzalutamide, cabazitaxel, and Radium-223.

However, enzalutamide showed a significant advantage over the other treatments in delaying PSA progression, suggesting it may be more effective in managing disease progression despite similar overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials. Tassinari, D., Cherubini, C., Roudnas, B., et al.[2021]

Access to life-prolonging therapies for metastatic castrate-resistant prostate cancer (mCRPC) varies significantly across Canadian provinces, with some therapies like abiraterone acetate and enzalutamide being funded in certain settings but not for sequential use.

Ra-223 and cabazitaxel have inconsistent funding across provinces, which could lead to disparities in patient survival and quality of life, highlighting the need for further research on the impact of these access inequalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disparity in public funding of therapies for metastatic castrate-resistant prostate cancer across Canadian provinces. Woon, DTS., Chandrasekar, T., Aaron, L., et al.[2020]

In a phase III trial involving 1195 patients with metastatic castration-resistant prostate cancer, abiraterone acetate significantly improved overall survival compared to prednisone, and this benefit was also reflected in health-related quality of life (HRQoL) scores.

Patients receiving abiraterone experienced significant improvements in their quality of life, with 48% reporting better scores on the FACT-P questionnaire compared to 32% for those on prednisone, and a longer median time before their quality of life worsened.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy. Harland, S., Staffurth, J., Molina, A., et al.[2018]

In a study involving 1173 patients with metastatic castration-sensitive prostate cancer, the combination of abiraterone, docetaxel, and androgen deprivation therapy significantly improved both overall survival and radiographic progression-free survival compared to standard treatments alone.

While the addition of abiraterone increased the incidence of grade 3 or worse adverse events, particularly hypertension, it did not raise the rates of other serious side effects like neutropenia or fatigue, suggesting a manageable safety profile for this triplet therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Fizazi, K., Foulon, S., Carles, J., et al.[2022]

In a study of 82 patients with metastatic castration-resistant prostate cancer who did not respond to docetaxel chemotherapy, 43% achieved a significant reduction in prostate-specific antigen (PSA) levels, indicating a positive response to treatment with abiraterone acetate and prednisolone.

The treatment resulted in a median overall survival of 11.8 months, with manageable side effects, the most common being bone pain, suggesting that this combination therapy is a viable second-line option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisolone for metastatic castration-resistant prostate cancer failing androgen deprivation and docetaxel-based chemotherapy: a phase II bridging study in Korean and Taiwanese patients. Kwak, C., Wu, TT., Lee, HM., et al.[2022]

In a study of 54 men with metastatic castration-resistant prostate cancer (mCRPC) who were treated with abiraterone, only 26% showed a significant decline in prostate-specific antigen (PSA) levels after receiving docetaxel, indicating limited efficacy of docetaxel following abiraterone treatment.

Patients who were refractory to abiraterone did not respond to docetaxel, suggesting that prior treatment with abiraterone may negatively impact the effectiveness of subsequent docetaxel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? Mezynski, J., Pezaro, C., Bianchini, D., et al.[2023]

Adding docetaxel or abiraterone to androgen-deprivation therapy (ADT) significantly improves overall survival in men with newly diagnosed metastatic prostate cancer, based on evidence from multiple studies involving thousands of participants.

The strongest survival benefits from docetaxel are observed in patients with high-volume metastatic disease, while abiraterone also shows similar benefits in high-risk patients, indicating both treatments are effective options alongside ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Morris, MJ., Rumble, RB., Basch, E., et al.[2019]

Cabazitaxel, abiraterone, and enzalutamide have been shown to significantly prolong overall survival in men with metastatic castration-resistant prostate cancer who have previously undergone chemotherapy, based on randomized phase 3 clinical trials.

The introduction of these new treatments has led to their approval and reimbursement in Belgium, marking an important advancement in options for patients with docetaxel-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New treatments for castration-resistant prostate cancer]. Sautois, B., Gennigens, C.[2021]

The study evaluated the effectiveness of abiraterone acetate combined with prednisone (AA+P) in 53 patients with castration-resistant prostate cancer (mCRPC), showing a good response to this treatment.

Key factors associated with higher survival rates included a longer duration of prostate cancer prior to treatment, lower pain intensity, extended treatment duration with AA+P, and favorable tumor marker levels at 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors. Jimenez Romero, ME., Gallego, MC., Navarro Serrato, JC., et al.[2021]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Concomitant use of abiraterone acetate and triptorelin in patients with castration-resistant prostate cancer]. [2018]

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

Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial. [2023]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic, Castration-resistant, Docetaxel-resistant Prostate Cancer: A Systematic Review of Literature With a Network Meta-analysis of Randomized Clinical Trials. [2021]

4. Canada pubmed.ncbi.nlm.nih.gov

Disparity in public funding of therapies for metastatic castrate-resistant prostate cancer across Canadian provinces. [2020]

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

Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy. [2018]

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

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Abiraterone acetate and prednisolone for metastatic castration-resistant prostate cancer failing androgen deprivation and docetaxel-based chemotherapy: a phase II bridging study in Korean and Taiwanese patients. [2022]

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

Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? [2023]

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

Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline. [2019]

10. Belgium pubmed.ncbi.nlm.nih.gov

[New treatments for castration-resistant prostate cancer]. [2021]

11. Greece pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors. [2021]