M9241 + SBRT for Prostate Cancer

Overseen By Willie C Jackson

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: ADT

Must not be taking: Systemic corticosteroids, Immunosuppressive medications

Disqualifiers: Metastatic disease, Previous prostatectomy, Autoimmune diseases, HIV, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

65 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Prostate cancer is often treated with radiation and ADT (ADT is androgen deprivation therapy). Up to 30% of these cancers recur within 5 years of treatment. Researchers want to see if a new drug (M9241) can help the immune system to fight prostate cancer. Objective: To find what doses of M9241 are safe in people who are treated for prostate cancer. Also, to see what effects M9241 has on the immune system. Eligibility: People aged 18 and older with high- and intermediate-risk prostate cancer. Their cancer must not have spread to other parts of the body. Design: The study will last 7 months. Participants will be screened. They will share their medical history. They will also have: \<TAB\>A physical exam \<TAB\>Routine blood and urine tests \<TAB\>Imaging scans of the chest, abdomen, and pelvis \<TAB\>A bone scan \<TAB\>A tumor biopsy \<TAB\>A specialized MRI. Participants will lie face down on the MRI scanner table. An antenna that receives a signal may be placed in the rectum. All participants will be treated with radiation therapy and ADT. Some participants will also receive M9241 as an injection under the skin. This treatment will start 4 weeks after the radiation has ended. Participants will receive a total of 3 doses. The injections will be 4 weeks apart. Some screening tests will be repeated at each visit. Participants who do not receive M9241 will also have screening tests during the treatment period. Participants will return for follow-up about 1 month after the last treatment or set of tests.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or immunosuppressive medications, you may need to adjust your treatment, as these are generally not allowed unless they are low-dose or inhaled steroids.

What data supports the effectiveness of the treatment M9241 + SBRT for Prostate Cancer?

Research shows that stereotactic body radiation therapy (SBRT) is increasingly used and considered safe and effective for treating low- and intermediate-risk prostate cancer, with studies reporting positive patient-reported quality of life outcomes. However, evidence for its use in high-risk prostate cancer is less solid, and there is no direct data on the combination with M9241. ^{1 2 3 4 5}

Is the combination of M9241 and SBRT safe for humans?

Stereotactic body radiation therapy (SBRT) has been shown to be safe for treating prostate cancer, with studies confirming its safety and effectiveness. However, specific safety data for the combination of M9241 (also known as NHS-IL12) with SBRT is not provided in the available research. ^{6 7 8 9 10}

How is the treatment M9241 + SBRT for prostate cancer different from other treatments?

The treatment M9241 + SBRT for prostate cancer is unique because SBRT delivers high-dose radiation in fewer sessions (usually 5 or less), making it a shorter and more convenient option compared to traditional radiotherapy, which requires many more sessions. This approach may offer radiobiologic advantages and improved survival outcomes for certain prostate cancer patients. ^{3 11 12 13 14}

Research Team

Ravi A Madan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Men over 18 with intermediate or high-risk prostate cancer that hasn't spread are eligible. They need to have certain levels of blood cells, liver and kidney function, and agree to use contraception. Excluded are those with HIV, active hepatitis, other recent cancers (except some skin/cervical/breast/prostate), previous prostate treatments, immune deficiencies/autoimmune diseases, allergies to M9241 or SBRT contraindications.

Inclusion Criteria

My prostate cancer can be biopsied.

I am a man aged 18 or older.

Testosterone greater than 100 ng/dL

Exclusion Criteria

I don't have conditions like inflammatory bowel disease that prevent SBRT.

I have started hormone therapy or radiation treatment before joining this trial.

I haven't had any cancer except for treatable ones in the last 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Radiation Therapy

Participants receive Stereotactic Body Radiation Therapy (SBRT) along with Androgen Deprivation Therapy (ADT)

4 weeks

Weekly visits (in-person)

Immunotherapy Treatment

Participants receive M9241 injections every 4 weeks for 3 doses, starting 4 weeks after radiation ends

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• M9241
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The trial tests if the drug M9241 can boost the immune system against prostate cancer when added to standard radiation therapy and ADT. Participants will receive either just radiation and ADT or these plus three doses of M9241 injections after radiation ends. The study lasts 7 months with follow-ups for safety and effectiveness.

Participant Groups

Group I: 3/Arm 2b Experimental Treatment 1 Intervention

SBRT

Group II: 2/Arm 2a Experimental Treatment 2 Interventions

Highest tolerated dose of M941+SBRT

Group III: 1/Arm 1 Experimental Treatment 2 Interventions

De-escalating doses of M9241 if appropriate + SBRT

Stereotactic Body Radiation Therapy (SBRT) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in European Union as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in Canada as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in Japan as Stereotactic Body Radiation Therapy for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 26 patients with low- or intermediate-risk prostate adenocarcinoma, stereotactic body radiation therapy (SBRT) showed excellent biochemical control with no observed failures after a median follow-up of 59.5 months.

The treatment resulted in manageable late toxicity, with only 11.5% of patients experiencing significant genitourinary or gastrointestinal side effects, and patient-reported quality of life remained stable compared to pre-treatment levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial. Maas, JA., Dobelbower, MC., Yang, ES., et al.[2023]

Stereotactic body radiotherapy (SBRT) is a recognized treatment for low- and intermediate-favorable risk prostate cancer, but its effectiveness for unfavorable and high-risk cases is less established.

The review highlights the complexity of comparing SBRT techniques due to the various treatment variations reported, indicating a need for more solid evidence in high-risk prostate cancer applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the current role of stereotactic body radiotherapy in the treatment of unfavorable intermediate- and high-risk prostate cancer. Mezeckis, M., Danny, V., Vladyslav, B., et al.[2023]

Stereotactic body radiotherapy (SBRT) for patients with metastatic castration-resistant prostate cancer (mCRPC) and oligoprogression (≤ 5 metastases) during androgen receptor-targeted therapy (ARTT) showed promising outcomes, with median time to next-line systemic treatment of 16.97 months and overall survival of 38.3 months based on a study of 34 patients.

The treatment was found to be safe, as no patients experienced significant toxicity (grade ≥ 2), indicating that SBRT can be an effective option for managing disease progression in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy. Ingrosso, G., Detti, B., Fodor, A., et al.[2021]

In a study of 174 hormone-naïve patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT), significant urinary symptoms were reported more frequently than bowel symptoms, with 51.6% of patients experiencing a clinically significant decline in urinary scores at 12 months.

The study indicates that while urinary and bowel symptoms initially increased after treatment, the proportion of patients reporting significant declines in these symptoms decreased from 12 to 36 months, suggesting potential late improvements in quality of life following SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Prostate Cancer: What is the Appropriate Patient-Reported Outcome for Clinical Trial Design? Woo, JA., Chen, LN., Wang, H., et al.[2020]

Stereotactic body radiotherapy (SBRT) for low- and intermediate-risk prostate cancer patients was found to be safe and well-tolerated, with mild acute toxicity reported in only a small number of cases (23 out of 72 for rectal and 50 out of 72 for urinary issues).

Patient-reported quality of life remained stable over the first year post-treatment, with minimal changes in urinary, rectal, sexual, and hormonal scores, indicating that SBRT does not significantly impact these aspects of life in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy with flattening filter-free beams for prostate cancer: assessment of patient-reported quality of life. Scorsetti, M., Alongi, F., Clerici, E., et al.[2021]

Stereotactic body radiation therapy (SBRT) resulted in significantly lower post-treatment PSA levels compared to intensity-modulated radiation therapy (IMRT) at 2 and 3 years, indicating better efficacy in controlling prostate cancer.

Both SBRT and IMRT showed similar overall survival rates after 5 years, but SBRT offers advantages such as lower cost and easier application, making it a suitable alternative for treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy versus conventional intensity-modulated radiation therapy for the treatment of prostate cancer]. Gao, QN.[2022]

Stereotactic body radiotherapy (SBRT) is shown to be safe and effective for treating node-positive prostate cancer, with a median follow-up of 30 months revealing no severe gastrointestinal toxicities and manageable genitourinary side effects.

In a study of 60 patients, SBRT resulted in a 3-year overall survival rate of 89% and a biochemical failure-free survival rate of 77%, indicating promising long-term outcomes even in patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. Telkhade, T., Murthy, V., Kanala, TS., et al.[2021]

A study involving 803 patients analyzed the quality of life (QOL) impacts of SBRT, IMRT, and brachytherapy for localized prostate cancer, showing that all treatments resulted in good QOL two years post-treatment.

SBRT demonstrated similar outcomes to IMRT in urinary and sexual domains, but showed a significant improvement in bowel symptoms compared to brachytherapy, suggesting it may be a safer option with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy. Evans, JR., Zhao, S., Daignault, S., et al.[2022]

In a study of 23 patients with high-risk prostate cancer, stereotactic body radiation therapy (SBRT) was found to be feasible and well tolerated, with low rates of severe gastrointestinal (GI) and genitourinary (GU) toxicities.

The treatment resulted in acute grade 1 GI toxicities in only 9.1% of patients and grade 3 GU toxicities in 4.5%, indicating that serious side effects were uncommon, but further long-term follow-up is needed to assess ongoing safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. Pinitpatcharalert, A., Happersett, L., Kollmeier, M., et al.[2022]

The use of stereotactic body radiation therapy (SBRT) for low and intermediate risk prostate cancer increased dramatically from 0.9% in 2004 to 19.5% in 2015, indicating growing acceptance of this treatment method.

SBRT has been shown to have a favorable toxicity profile and efficacy, leading to a significant decline in conventional fractionation treatments, which dropped from 96.3% to 75.8% during the same period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current use of stereotactic body radiation therapy for low and intermediate risk prostate cancer: A National Cancer Database Analysis. Malouff, TD., Stross, WC., Seneviratne, DS., et al.[2021]

In a phase II study involving 55 patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) delivering 36 Gy in 4 fractions demonstrated a high 3-year biochemical control rate of 89.8%, indicating its efficacy in managing the disease.

The treatment was generally safe, with only 9% of patients experiencing acute grade 2 genitourinary toxicities and 11% experiencing gastrointestinal toxicities, while no severe grade 3 or higher toxicities were reported. Quality of life scores showed a slight decrease during treatment but recovered within 3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer. Kawakami, S., Tsumura, H., Satoh, T., et al.[2022]

Stereotactic body radiotherapy (SBRT) is emerging as a treatment option for localized prostate cancer, but the evidence supporting its use is still incomplete due to variability in clinical studies.

There is inconsistency in treatment techniques, target volumes, and dose constraints across different studies, highlighting the need for standardized protocols in SBRT for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly hypofractionated schedules for localized prostate cancer: Recommendations of the GETUG radiation oncology group. Lapierre, A., Hennequin, C., Beneux, A., et al.[2022]

In a study of 28,028 men with unfavorable-intermediate-risk prostate cancer, stereotactic body radiotherapy (SBRT) was associated with improved overall survival compared to conventionally fractionated radiotherapy (CFRT) without androgen deprivation therapy (ADT), suggesting its effectiveness as a treatment option.

SBRT offers a shorter and less expensive treatment course, which may reduce patient exposure to COVID-19, and is recommended as a viable alternative for prostate cancer treatment, although further clinical trials are needed to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propensity-Weighted Survival Analysis of SBRT vs. Conventional Radiotherapy in Unfavorable Intermediate-Risk Prostate Cancer. Andruska, N., Fischer-Valuck, BW., Agabalogun, T., et al.[2023]

Stereotactic body radiotherapy (SBRT) for localized prostate cancer shows promising results, with studies indicating that ultra-hypofractionated schedules (like 42.7 Gy in 7 fractions) are non-inferior to standard treatments in terms of 5-year biochemical recurrence-free survival and have similar tolerability.

Current evidence suggests that two-fraction SBRT may be the shortest effective treatment schedule, but caution is advised against single-fraction SBRT due to concerns about inferior efficacy, highlighting the need for ongoing trials to determine optimal fractionation schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus? Ong, WL., Loblaw, A.[2023]

References

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

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial. [2023]

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

Overview of the current role of stereotactic body radiotherapy in the treatment of unfavorable intermediate- and high-risk prostate cancer. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Prostate Cancer: What is the Appropriate Patient-Reported Outcome for Clinical Trial Design? [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy with flattening filter-free beams for prostate cancer: assessment of patient-reported quality of life. [2021]

6. China pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy versus conventional intensity-modulated radiation therapy for the treatment of prostate cancer]. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. [2021]

8. Ireland pubmed.ncbi.nlm.nih.gov

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy. [2022]

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

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Current use of stereotactic body radiation therapy for low and intermediate risk prostate cancer: A National Cancer Database Analysis. [2021]

11. England pubmed.ncbi.nlm.nih.gov

A phase II trial of stereotactic body radiotherapy in 4 fractions for patients with localized prostate cancer. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Highly hypofractionated schedules for localized prostate cancer: Recommendations of the GETUG radiation oncology group. [2022]

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

Propensity-Weighted Survival Analysis of SBRT vs. Conventional Radiotherapy in Unfavorable Intermediate-Risk Prostate Cancer. [2023]

14. Germany pubmed.ncbi.nlm.nih.gov

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus? [2023]