SBRT + Pluvicto for Prostate Cancer

(STARLiT Trial)

Overseen By Angela Y Jia, MD, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Angela Y. Jia, MD PhD

Must not be taking: Spironolactone, Chemotherapy, Estrogens, others

Disqualifiers: Metastatic disease, Prior prostate treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

45 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to is to investigate if it is possible to lower the chance of cancer reoccurrence and also preserve quality of life by using the drug Pluvicto instead of androgen-deprivation therapy to the usual radiation therapy for advanced local prostate cancer. Participants will receive one dose of Pluvicto, followed by radiation about 6 weeks later. Radiation therapy will be completed in 5 treatments over the period of 2 weeks. A second dose of Pluvicto will be given 6 weeks after radiation is complete. Some participants may also receive a third dose of Pluvicto, and this would be given 6 weeks after the second dose of Pluvicto.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as spironolactone and other investigational drugs, 30 days before starting the study treatment. Additionally, oral ketoconazole, chemotherapy, immunotherapy, estrogens, and radiopharmaceuticals must be stopped 3 months before joining the trial and during the study treatment.

What data supports the effectiveness of the treatment SBRT + Pluvicto for prostate cancer?

Research shows that stereotactic body radiation therapy (SBRT) is effective for treating various stages of prostate cancer, including localized and oligometastatic cases, with good survival outcomes and low side effects. This suggests that SBRT, as part of the combined treatment with Pluvicto, could be beneficial for prostate cancer patients. ^{1 2 3 4 5}

Is SBRT safe for prostate cancer treatment?

SBRT (Stereotactic Body Radiation Therapy) for prostate cancer is generally considered safe, with most patients experiencing mild to moderate side effects like urinary and bowel issues, which are usually temporary. Serious side effects are rare. ^{6 7 8 9 10}

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

SBRT (Stereotactic Body Radiation Therapy) is a precise form of radiation therapy that targets prostate cancer with high doses in fewer sessions, which can be more convenient and potentially less harmful to surrounding tissues compared to traditional radiation therapy. Pluvicto, when combined with SBRT, may offer a novel approach by enhancing the effectiveness of the treatment, although specific details about this combination are not provided in the research. ^{4 11 12 13 14}

Research Team

Angela Y Jia, MD, PhD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Daniel E Spratt, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for men with advanced local prostate cancer who haven't had hormone therapy yet. They should be fit for radiation treatment and willing to potentially delay hormone therapy. People can't join if they've already had certain treatments, have other cancers, or conditions that could interfere with the study.

Inclusion Criteria

I am healthy enough for treatment and agree to follow-up appointments.

Ability to understand and the willingness to sign a written informed consent

My prostate cancer has been confirmed through a biopsy.

Exclusion Criteria

Any condition that in the opinion of the investigator would preclude participation in this study

I cannot undergo PSMA/PET scans due to health reasons.

I haven't taken any prohibited medications recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive one dose of Pluvicto followed by radiation therapy

8 weeks

1 visit for Pluvicto, 5 visits for radiation

Second Treatment

Participants receive a second dose of Pluvicto 6 weeks after radiation

6 weeks

Optional Third Treatment

Some participants may receive a third dose of Pluvicto 6 weeks after the second dose

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lu-PSMA-617
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The trial tests Pluvicto (Lu-PSMA-617) combined with Stereotactic Body Radiation Therapy (SBRT). Participants get one dose of Pluvicto, followed by a series of five radiation treatments over two weeks, then possibly up to two more doses of Pluvicto at six-week intervals.

Participant Groups

Group I: Lu-PSMA-617 + SBRT Experimental Treatment 2 Interventions

* Lu-PSMA-617: 7.4GBq intravenous infusion once with cycle 1, followed by 7.4GBq cycle 2 that is delivered 6 weeks after SBRT , and potentially 7.4GBq cycle #3 delivered 6 weeks after cycle #2 pending dose escalation * Radiation therapy: 5 fractions to prostate and elective nodal irradiation, SBRT, delivered 6 weeks after cycle 1 of 177Lu-PSMA-617

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?

Angela Y. Jia, MD PhD

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

Stereotactic body radiotherapy (SBRT) for localized prostate cancer showed a 5-year biochemical relapse-free survival (bRFS) rate of 93% across 1100 patients, indicating its effectiveness as a treatment option.

The study found no significant differences in outcomes based on the use of androgen deprivation therapy or total radiation dose, suggesting that SBRT is a robust treatment regardless of these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for localized prostate cancer: pooled analysis from a multi-institutional consortium of prospective phase II trials. King, CR., Freeman, D., Kaplan, I., et al.[2022]

In a phase I/II clinical trial involving 91 prostate cancer patients, stereotactic body radiation therapy (SBRT) demonstrated excellent long-term efficacy, with a 98.6% freedom from biochemical failure at 5 years and 100% distant metastasis-free survival.

While SBRT was effective, higher doses (greater than 47.5 Gy) were associated with increased severe late toxicity, highlighting the need for careful dose management to minimize adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial. Hannan, R., Tumati, V., Xie, XJ., et al.[2022]

In a study of 713 men treated with stereotactic body radiation therapy (SBRT) for localized prostate cancer, only 3% to 4% experienced significant long-term declines in health-related quality of life (HRQOL), indicating that SBRT has minimal long-term negative effects on overall well-being.

Factors such as lower baseline bowel HRQOL and depression were found to predict declines in HRQOL, suggesting that comorbid conditions may play a larger role in patient outcomes than the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of multidomain decline in health-related quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer. Dess, RT., Jackson, WC., Suy, S., et al.[2022]

In a prospective phase II trial involving 110 patients aged 70 and older with localized prostate cancer, stereotactic body radiotherapy (SBRT) demonstrated a severe toxicity rate of less than 5%, confirming its safety for this patient population.

The SBRT regimen resulted in a biochemical progression-free survival (bPFS) rate of 90% over a median follow-up of 36 months, indicating its efficacy in treating localized prostate cancer without negatively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial. Nguyen, P., Harzée, L., Retif, P., et al.[2022]

In a study of 66 prostate cancer patients treated with ultra-hypofractionated stereotactic body radiation therapy (SBRT), the treatment demonstrated excellent biochemical control, with a 2-year freedom from biochemical failure (FFBF) rate of 88.4%.

The treatment was associated with low toxicity, as no patients experienced severe (grade ≥3) genitourinary toxicity, and only 13.6% experienced grade 2 toxicities, indicating that SBRT is a safe option for postoperative prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes of postoperative ultra-hypofractionated stereotactic body radiotherapy in prostate cancer. Ozyigit, G., Onal, C., Beduk Esen, CS., et al.[2023]

Stereotactic body radiation therapy (SBRT) for localized prostate cancer showed similar 5-year survival rates (90.8% for SBRT vs. 88.1% for IMRT) and comparable freedom from biochemical failure (FFBF) rates, indicating its efficacy is on par with intensity-modulated radiation therapy (IMRT).

Both treatment methods had low toxicity, with no severe (grade 3 or higher) side effects reported, suggesting that SBRT is a safe alternative that offers the benefits of shorter treatment duration and lower costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propensity score matched comparison of SBRT versus IMRT for the treatment of localized prostate cancer. Oliai, C., Bernetich, M., Brady, L., et al.[2022]

Between 2006 and 2020, there was a significant increase in publications and citations related to stereotactic body radiotherapy (SBRT) for prostate cancer, indicating growing interest and research in this treatment method.

The United States led the research output in this field, with a focus on SBRT applications in oligometastatic disease, reirradiation, and salvage therapy, highlighting key areas for future investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Prostate Cancer: Where, When, and Who? A Bibliometric Analysis. Viani, GA., Gouveia, AG., Jacinto, AA., 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]

In a study of 17 men with oligometastatic prostate cancer treated with stereotactic body radiation therapy (SBRT), local control was achieved in 100% of cases, and over half of the patients (53%) had an undetectable prostate-specific antigen (PSA) after treatment.

The treatment was well-tolerated, with only mild toxicities reported and no severe side effects (grade ≥3), indicating that SBRT is a safe and effective option for managing oligometastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy in the treatment of oligometastatic prostate cancer. Ahmed, KA., Barney, BM., Davis, BJ., et al.[2022]

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]

References

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

Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for localized prostate cancer: pooled analysis from a multi-institutional consortium of prospective phase II trials. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial. [2022]

5. Poland pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for oligometastatic prostate cancer. [2022]

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

Predictors of multidomain decline in health-related quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial. [2022]

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

Treatment outcomes of postoperative ultra-hypofractionated stereotactic body radiotherapy in prostate cancer. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Propensity score matched comparison of SBRT versus IMRT for the treatment of localized prostate cancer. [2022]

10. Hungary pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy with CyberKnife accelerator for low- and intermediate risk prostate cancer]. [2019]

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

Stereotactic Body Radiotherapy for Prostate Cancer: Where, When, and Who? A Bibliometric Analysis. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

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

13. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy in the treatment of oligometastatic prostate cancer. [2022]

14. 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]