Radiation + Androgen Suppression for Prostate Cancer

Recruiting at 5 trial locations

Overseen By Matthew Morocco

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Proton Collaborative Group

Must not be taking: Anticoagulants

Disqualifiers: Previous prostate surgery, Pelvic radiation, Androgen 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

Duration: 6 months

192 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain blood thinners like warfarin or Plavix unless they can be stopped for treatment-related reasons.

What data supports the effectiveness of the treatment Radiation + Androgen Suppression for Prostate Cancer?

Research shows that combining androgen deprivation therapy (ADT) with proton beam therapy (PBT) benefits patients with intermediate- and high-risk prostate cancer. Additionally, PBT has been shown to reduce the dose to normal tissues, potentially minimizing side effects while effectively targeting the tumor. ^{1 2 3 4 5}

Is the combination of radiation and androgen suppression therapy safe for prostate cancer treatment?

Studies show that proton beam therapy (a type of radiation) for prostate cancer generally has manageable side effects, with some patients experiencing mild to moderate issues like gastrointestinal and genitourinary problems. Combining it with androgen deprivation therapy (hormone therapy) is common, but the exact safety profile can vary, so discussing personal risks with a doctor is important. ^{1 2 3 6 7}

How is proton beam therapy different from other treatments for prostate cancer?

Proton beam therapy (PBT) is unique because it uses protons to deliver high doses of radiation directly to the prostate tumor while minimizing exposure to surrounding healthy tissues, thanks to its precise dose deposition properties. This can potentially reduce side effects compared to traditional X-ray radiation therapies. ^{2 4 8 9 10}

What is the purpose of this trial?

The purpose of this study is to compare the effects, good and/or bad of two treatment methods on subjects and their cancer. Proton beam radiation therapy is one of the treatments for men with prostate cancer who have localized disease. The benefit of the combination with androgen suppression is not completely understood. This study will compare the use of hypofraction proton therapy (28 treatments) alone to proton therapy with androgen suppression therapy.

Research Team

Carlos Vargas, MD

Principal Investigator

Proton Collaborative Group

Eligibility Criteria

Men with intermediate-risk prostate cancer who have not had previous prostate surgery, androgen suppression therapy, or pelvic radiation. They must be in good physical condition (ECOG 0-1), have a Gleason Score of 7, PSA levels between 10-20 ng/ml, T stage T2b-T2c, and no major medical issues that could affect the study.

Inclusion Criteria

My prostate cancer has a Gleason score between 2 and 7, based on more than 6 biopsy samples.

My PSA level is 20 ng/ml or lower, measured within the last 3 months.

I can start treatment within 56 days of being chosen for the trial.

Exclusion Criteria

Major medical, addictive or psychiatric illness which in the investigator's opinion, will prevent the consent process, completion of the treatment and/or interfere with follow-up (Consent by legal authorized representative is not permitted for this study)

I had a heart attack in the last 6 months.

My pelvic lymph nodes are enlarged but have tested negative for cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hypofraction proton therapy alone or with androgen suppression therapy

6 months

28 treatments (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Annual visits (in-person)

Treatment Details

Interventions

• Androgen Suppression Therapy
• Proton Beam Radiation Therapy

Trial Overview The trial is testing hypofraction proton therapy alone versus proton therapy combined with androgen suppression. Participants will receive either just the radiation treatment or both treatments to see which is more effective at treating localized prostate cancer.

Participant Groups

Group I: Radiation + Androgen Suppression Experimental Treatment 2 Interventions

Androgen Suppression Therapy x 6 months + Radiation

Group II: Radiation Alone Active Control 1 Intervention

Proton Radiation Total Dose=70 Gy(RBE) OR High Dose Radiation with IMRT Alone=81 Gy OR Intraoperative LDR Brachytherapy and IMRT=45 Gy

Proton Beam Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in United States as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Canada as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Japan as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in China as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Switzerland as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Who Is Running the Clinical Trial?

Proton Collaborative Group

Lead Sponsor

Trials

10

Recruited

41,100+

Findings from Research

In a study of 192 prostate cancer patients treated with proton beam therapy (PBT) over a median follow-up of 1.7 years, only 5 patients experienced grade 3 toxicity, with no occurrences of grade 4 or 5 toxicity, indicating a high safety profile for this treatment.

Patient-reported outcomes showed stable urinary function post-treatment, while sexual health scores declined slightly at 1 year but did not worsen thereafter; bowel function scores also decreased but stabilized, suggesting manageable side effects associated with PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. Lee, HJ., Macomber, MW., Spraker, MB., et al.[2019]

In intermediate-risk prostate cancer patients (520 participants), androgen deprivation therapy (ADT) significantly improved biochemical relapse-free rates, particularly in those with multiple risk factors, indicating that short-term ADT (≤6 months) is beneficial.

For high-risk prostate cancer patients (555 participants), longer ADT durations (>6 months) were associated with better biochemical relapse-free rates, especially for those with multiple high-risk factors, suggesting that ADT for ≥21 months may be optimal when combined with high-dose proton beam therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. Murakami, M., Ishikawa, H., Shimizu, S., et al.[2020]

In a study of 289 prostate cancer patients, hypofractionated proton beam therapy (PBT) showed no significant differences in acute adverse event rates or quality of life, as measured by the International Prostate Symptom Score (IPSS), compared to conventionally fractionated PBT.

The study evaluated patients treated with different doses (2.0, 2.5, and 3.0 Gy RBE per fraction) and found that factors like diabetes, age, and androgen deprivation therapy did not influence the IPSS outcomes, suggesting that hypofractionated PBT is a safe option without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. Iizumi, T., Ishikawa, H., Sekino, Y., et al.[2022]

In a study of 180 prostate cancer patients treated between 1972 and 1979, those receiving a proton beam boost along with conventional x-ray therapy were able to receive a higher dose to the tumor without increasing side effects, demonstrating the safety of this approach.

Despite the increased dose delivered to the tumor using the proton beam, there were no significant differences in patient survival, disease-free survival, or local recurrence-free survival compared to those treated with conventional x-ray therapy, suggesting similar efficacy between the two methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison. Duttenhaver, JR., Shipley, WU., Perrone, T., et al.[2019]

In a study of 276,880 men with localized prostate cancer, proton beam therapy (PBT) was associated with significantly better overall survival (OS) compared to photon-based external-beam radiation therapy (EBRT), with an adjusted hazard ratio of 1.72, indicating a higher risk of worse outcomes with EBRT.

PBT showed similar OS outcomes to brachytherapy (BT), particularly benefiting younger men (≤ 65 years) with low-risk disease, suggesting that PBT may be a more effective treatment option for certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival After Treatment of Localized Prostate Cancer With Proton Beam Therapy, External-Beam Photon Therapy, or Brachytherapy. Liu, Y., Patel, SA., Jani, AB., et al.[2021]

Proton beam therapy (PBT) as a standalone treatment for localized prostate cancer showed a high 5-year progression-free survival rate of 97% for intermediate-risk patients and 83% for high-risk patients, indicating its efficacy.

The treatment was associated with low rates of severe side effects, with only 3.9% of patients experiencing significant gastrointestinal toxicity and 23.5% experiencing acute genitourinary toxicity, suggesting that PBT can effectively preserve patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study. Arimura, T., Yoshiura, T., Matsukawa, K., et al.[2020]

In a study of 27,647 Medicare beneficiaries with prostate cancer, proton radiotherapy (PRT) was associated with lower genitourinary toxicity at 6 months compared to intensity-modulated radiotherapy (IMRT), but this difference disappeared by 12 months post-treatment.

PRT was significantly more expensive than IMRT, with median Medicare reimbursements of $32,428 for PRT compared to $18,575 for IMRT, yet no long-term differences in toxicity were observed between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton versus intensity-modulated radiotherapy for prostate cancer: patterns of care and early toxicity. Yu, JB., Soulos, PR., Herrin, J., et al.[2022]

Proton beam therapy (PBT) allows for higher radiation doses to be delivered to prostate cancer tissues while reducing exposure to surrounding healthy organs, making it a safer option for treatment.

Interest in PBT is growing due to improvements in treatment delivery systems and increased availability, highlighting the need for a comprehensive understanding of its effectiveness and technical aspects in treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for the treatment of prostate cancer. Pugh, TJ., Lee, AK.[2018]

Proton radiation therapy is gaining popularity for localized prostate cancer due to its ability to deliver high doses to the tumor while minimizing damage to surrounding healthy tissue, thanks to the unique Bragg peak effect.

While proton therapy has shown effectiveness in dose escalation for prostate cancer, it currently lacks clear dosimetric superiority over traditional X-ray intensity-modulated radiation therapy, although advancements in techniques like pencil-beam scanning may enhance its benefits in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation for localized prostate cancer. Coen, JJ., Zietman, AL.[2021]

In a study involving 150 patients with low- and intermediate-risk prostate cancer, conformal proton therapy did not significantly alter serum testosterone levels within 24 months after treatment.

The median testosterone levels remained stable post-treatment, indicating that proton therapy may not have the same testosterone-suppressing effects observed with traditional x-ray radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for prostate cancer is not associated with post-treatment testosterone suppression. Nichols, RC., Morris, CG., Hoppe, BS., et al.[2022]

References

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

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. [2020]

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

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. [2022]

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

Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison. [2019]

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

Overall Survival After Treatment of Localized Prostate Cancer With Proton Beam Therapy, External-Beam Photon Therapy, or Brachytherapy. [2021]

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

Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study. [2020]

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

Proton versus intensity-modulated radiotherapy for prostate cancer: patterns of care and early toxicity. [2022]

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

Proton beam therapy for the treatment of prostate cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Proton radiation for localized prostate cancer. [2021]

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

Proton radiotherapy for prostate cancer is not associated with post-treatment testosterone suppression. [2022]