Systemic + Local Therapy for Prostate Cancer

(VA STARPORT Trial)

Recruiting at 21 trial locations

Overseen By Caitlin C Authier, MPH MSW

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: VA Office of Research and Development

Must be taking: SST agents

Disqualifiers: Castration-resistant prostate cancer, Brain metastases, 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: 2 years

464 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for Veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants already on systemic therapy (SST) for prostate cancer can continue if they have been on it for 180 days. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination ADT + Abiraterone + Methylprednisolone for prostate cancer?

Research shows that adding abiraterone or docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic prostate cancer. Studies like STAMPEDE and LATITUDE have demonstrated that these combinations offer a survival benefit compared to ADT alone. ^{1 2 3 4 5}

Is the combination of ADT with abiraterone or docetaxel generally safe for humans?

The combination of ADT with abiraterone or docetaxel has been shown to improve survival in patients with metastatic prostate cancer and is considered to have acceptable overall tolerance, meaning it is generally safe for use in humans. ^{1 2 4 6 7}

What makes this prostate cancer treatment unique?

This treatment combines systemic and local therapies, including drugs like abiraterone and docetaxel, with androgen deprivation therapy (ADT) to improve survival in advanced prostate cancer. It offers a novel approach by using a combination of drugs that target different aspects of cancer growth, providing a more comprehensive treatment strategy compared to ADT alone. ^{1 2 4 8 9}

Research Team

Abhishek Solanki, MD MS

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Eligibility Criteria

This trial is for veterans with oligorecurrent prostate cancer, who've had prior local treatment and are experiencing a rise in PSA indicating recurrence. They must be able to consent, have an ECOG Performance Status of 2 or less, and meet specific criteria regarding their initial cancer stage and treatments. Those already on systemic therapy can join if it's been less than 180 days.

Inclusion Criteria

Ability to provide Informed Consent for participation in the study

I can take care of myself and am up and about more than half of my waking hours.

I had prostate cancer treated with the intent to cure and it might be coming back based on recent tests.

Exclusion Criteria

I have had cancer spread to my lymph nodes, bones, or organs after treatment meant to cure it, which may not make me eligible for certain targeted therapies.

My prostate cancer is resistant to hormone therapy, shown by rising PSA levels despite low testosterone.

I do not have brain metastases or specific malignant spinal conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Standard Systemic Therapy (SST) with or without PET-directed local therapy, including surgery or radiation to all metastases

2 years

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of progression-free survival and quality of life

4 years

Treatment Details

Interventions

• ADT + Abiraterone + Methylprednisolone
• ADT + Abiraterone + Prednisone
• ADT + Apalutamide
• ADT + Docetaxel +/- prednisone
• ADT + Enzalutamide
• ADT + Nilutamide, Flutamide, & Bicalutamide
• Degarelix
• Goserelin
• Histrelin
• Leuprolide
• PET-directed Local Therapy using Radiation
• PET-directed Local Therapy using Surgery
• Relugolix
• Triptorelin

Trial Overview The study tests whether adding PET-directed local therapy (radiation or surgery) to standard systemic therapy improves disease control in patients with recurring prostate cancer detected by PET/CT scans. It's a multi-institutional phase II/III randomized trial comparing two approaches.

Participant Groups

Group I: SST + PET-directed local therapy Experimental Treatment 12 Interventions

In addition to SST, all Veterans will receive PET-directed local therapy to all metastases using surgery or radiation. If De novo, Veterans will also receive prostate-directed radiation or radical prostatectomy to treat the prostate/prostate bed. The best course of treatment will be determined using shared decision-making between the physician and Veteran.

Group II: Standard Systemic Therapy (SST) Active Control 9 Interventions

All Veterans will receive SST (if De novo, Veterans will receive prostate-directed radiation).

ADT + Abiraterone + Methylprednisolone is already approved in United States, European Union for the following indications:

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study of 566 patients with advanced prostate cancer, adding abiraterone acetate with prednisolone (AAP) did not show a significant difference in overall survival compared to docetaxel with prednisolone (DocP), indicating both treatments are similarly effective.

Both treatment regimens had comparable safety profiles, with similar rates of severe adverse events, although the types of toxicities differed, aligning with the known effects of each drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Sydes, MR., Spears, MR., Mason, MD., 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 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]

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]

A systematic review of 6067 patients from five trials found that both abiraterone acetate plus ADT (Abi-ADT) and docetaxel plus ADT (Doce-ADT) significantly improved overall survival compared to ADT alone, with hazard ratios of 0.63 and 0.75 respectively.

There was no statistically significant difference in overall survival between Abi-ADT and Doce-ADT, but Bayesian analysis suggested an 89% probability that Abi-ADT might be the preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis. Wallis, CJD., Klaassen, Z., Bhindi, B., et al.[2019]

Adding docetaxel to androgen deprivation therapy (ADT) is recommended for fit patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), showing potential benefits in treatment outcomes.

Recent trials indicate that combining abiraterone acetate plus prednisone with ADT also provides a significant survival advantage and is well-tolerated, suggesting it should be considered a standard treatment option for mHSPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Guidelines for Metastatic Hormone-sensitive Prostate Cancer: Abiraterone Acetate Combined with Castration Is Another Standard. Mottet, N., De Santis, M., Briers, E., et al.[2020]

Recent trials have shown that combining enzalutamide or apalutamide with androgen deprivation therapy (ADT) significantly improves survival in patients with metastatic castration-sensitive prostate cancer, expanding treatment options beyond docetaxel and abiraterone acetate.

Emerging evidence also supports the use of radiotherapy for the primary tumor in metastatic prostate cancer, suggesting a more personalized approach to treatment based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving options in metastatic castration-sensitive prostate cancer. Hamilou, Z.[2021]

In a study of 196 men with metastasized hormone-sensitive prostate cancer, the combination of abiraterone acetate (AA) and androgen deprivation therapy (ADT) showed significantly longer progression-free survival (PFS1: 23 months vs. 13 months) and overall survival (OS: 80 months vs. 61 months) compared to docetaxel (D) and ADT.

Both treatment regimens had similar overall toxicity rates, suggesting that while AA+ADT may offer better progression-free outcomes, it does not increase the risk of adverse effects compared to D+ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer. Tsaur, I., Heidegger, I., Bektic, J., et al.[2022]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Updated Guidelines for Metastatic Hormone-sensitive Prostate Cancer: Abiraterone Acetate Combined with Castration Is Another Standard. [2020]

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

The evolving options in metastatic castration-sensitive prostate cancer. [2021]

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

A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer. [2022]

9. Belgium pubmed.ncbi.nlm.nih.gov

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