Standard Therapy + Surgery/Radiation for Prostate Cancer

Recruiting at 343 trial locations

Overseen By Amir Lavaf

Age: 18+

Sex: Male

Trial Phase: Phase 3

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 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

1273 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding surgery or radiation to standard prostate cancer treatments can help control cancer that has spread beyond the prostate. Participants will receive either standard treatments alone or with additional surgery or radiation to determine which approach is more effective. The trial seeks participants with prostate cancer that has spread, who have not received previous local treatments like radiation, and have been on standard therapy for no more than 28 weeks without cancer progression. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in prostate cancer treatment.

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.

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

Research shows that many treatments in this study have been tested for safety in humans. Here's a simple overview:

1. **Abiraterone**: Studies indicate that most participants experience some side effects, but these are not more severe than those from standard treatments.

2. **Bicalutamide**: Causes hot flashes in about 53% of patients, but it is generally safe and well-tolerated.

3. **Degarelix**: Poses a lower risk of heart problems compared to some other treatments, suggesting it is safe for many patients.

4. **Docetaxel**: Common side effects include hospital visits and a low white blood cell count with fever. Monitoring for these issues is important.

5. **Flutamide**: Has a higher chance of side effects that may lead to stopping treatment. About 12.8% of patients in studies had to stop due to side effects.

6. **Goserelin Acetate**: Can cause hot flashes and pain, but these are common and manageable. It is generally considered safe.

7. **Histrelin Acetate**: Mostly safe, with no deaths directly linked to the treatment in studies. It has a good safety profile for most patients.

8. **Leuprolide Acetate**: Well-tolerated with effective testosterone suppression. Most side effects are mild and resolve quickly.

9. **Nilutamide**: Generally safe and may help improve survival rates. Some benefits in disease progression and survival have been noted.

10. **Triptorelin**: Supports good safety and quality of life outcomes. Some side effects may occur, often related to the cancer itself.

Most of these treatments are already approved for prostate cancer or other conditions, demonstrating their general safety based on previous use. Participants in the trial will receive close monitoring and management of any side effects by the medical team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of standard systemic therapy (SST) with surgery or radiation for prostate cancer because it integrates multiple treatment modalities to potentially enhance outcomes. Unlike treatments that focus solely on hormone therapy or chemotherapy, this approach combines well-established drugs like abiraterone or leuprolide acetate with surgical removal of the prostate or targeted radiation. This multi-pronged strategy aims to attack the cancer from different angles, potentially improving survival rates and reducing recurrence. By leveraging both medical and surgical interventions, this protocol could provide a more comprehensive treatment for patients, offering hope for better control of the disease.

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

This trial will compare different treatment approaches for prostate cancer. Research has shown that prostate removal surgery, particularly with robotic assistance, can improve outcomes for prostate cancer patients. Studies indicate it may reduce complications and increase survival rates. For radiation therapy, research suggests it effectively treats prostate cancer, significantly decreasing cancer spread and extending patients' lives. In this trial, one group will receive standard systemic therapy (SST) alone, while another group will receive SST combined with either prostatectomy or radiation therapy. Both treatments have demonstrated positive results in managing prostate cancer when used with standard therapies. ^{6 7 8 9 10}

Who Is on the Research Team?

Brian Chapin

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Bicalutamide
• Degarelix
• Docetaxel
• Flutamide
• Goserelin Acetate
• Histrelin Acetate
• Leuprolide Acetate
• Nilutamide
• Orchiectomy
• Prednisone
• Radiation Therapy
• Radical Prostatectomy
• Triptorelin

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zytiga for:

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

Approved in European Union as Zytiga for:

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

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+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

Citations

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Intensity-modulated radiotherapy for prostate cancer - PMC Multiple clinical trials have demonstrated improved cancer outcomes with dose escalation, but toxicities using 3D-CRT and escalated doses have been problematic.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214122

Fifteen-Year Outcomes after Monitoring, Surgery, or ... After median follow-up of 15 years, 45 patients (2.7%) had died of prostate cancer: 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405630822001008

The role of image-guided radiotherapy in prostate cancer Radiotherapy contributes significantly to the treatment of prostate cancer, and it can cure 60 % of men with localized prostate cancer, which might benefit from ...

4. nature.com nature.com/articles/s41391-022-00535-4

Prostate cancer intensity-modulated radiotherapy and long ... Daily versus weekly prostate cancer image guided radiation therapy: phase 3 multicenter randomized trial. ... outcomes in prostate cancer: results ...

5. uclahealth.org uclahealth.org/news/release/study-confirms-safety-and-efficacy-higher-dose-per-day

Study confirms safety and efficacy of higher-dose-per-day ... A shorter, standard-dose course radiation treatment is just as effective as conventional radiotherapy for prostate cancer, without compromising the safety of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40940844/

The Safety of Abiraterone Acetate in Patients with Metastatic ... Nearly all participants experienced at least one adverse event (98.4% abiraterone, 97.3% standard of care [SOC]).

7. mdpi.com mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ... Conclusions: In this IPD meta-analysis, abiraterone acetate provides no greater risk of SAE in those receiving abiraterone than those receiving SOCs. Patients ...

8. e-juo.org e-juo.org/journal/view.php?number=594

Assessing Patient Risk, Benefit, and Outcomes in Drug ... Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint.

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704174

Abiraterone plus Prednisone in Metastatic, Castration- ... The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group ( ...

10. waocp.com waocp.com/journal/index.php/apjcb/article/view/1482

Real-World Clinical Outcomes of Low Dose versus ... Low-dose abiraterone seems to be comparable to standard-dose abiraterone in mCRPC with 75% lower financial cost.