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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Pluvicto (Lu-PSMA-617) can reduce the recurrence of prostate cancer while maintaining quality of life, as an alternative to the usual hormone therapy with radiation. Participants will receive doses of Pluvicto and undergo radiation therapy to assess the effectiveness of this combination. Men with prostate cancer that hasn't spread to distant parts of the body, confirmed by specific scans, and who haven't received previous cancer treatments might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works and measure its effectiveness in an initial, smaller group.

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.

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

Research has shown that Pluvicto® (also known as Lu-PSMA-617) is generally safe for patients with prostate cancer. Various studies have reported low levels of side effects, with most being mild, such as tiredness, dry mouth, and nausea. Serious side effects were rare.

Studies also indicate that Stereotactic Body Radiation Therapy (SBRT) is safe for treating prostate cancer. Most patients do not experience severe side effects. Some have reported mild urinary issues or nerve pain, but these are uncommon.

Previous research has demonstrated the safety of both treatments, suggesting they are likely to be safe for participants in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lu-PSMA-617 combined with Stereotactic Body Radiation Therapy (SBRT) because it offers a targeted approach for treating prostate cancer. Unlike traditional treatments like surgery, hormone therapy, or external beam radiation, Lu-PSMA-617 is a radioligand therapy that specifically targets the PSMA protein often found in high levels on prostate cancer cells. This targeted approach means that radiation is delivered directly to the cancer cells, potentially reducing damage to surrounding healthy tissue. Additionally, the treatment is administered in cycles, allowing for a controlled and potentially more effective attack on the cancer. This combination of precision and potential efficacy is what makes this treatment a promising option for patients.

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

Research has shown that Pluvicto, also known as Lu-PSMA-617, holds promise for treating prostate cancer. Studies have found that it can significantly reduce the risk of cancer progression or death. Patients receiving this treatment have generally responded well, with manageable side effects. Additionally, earlier trials demonstrated a significant drop in PSA levels, indicating its effectiveness.

Stereotactic Body Radiation Therapy (SBRT) has also succeeded in treating prostate cancer, offering high survival rates and symptom relief over five years. Patients undergoing SBRT have experienced few serious side effects, making it a safe option for many. In this trial, participants will receive a combination of Lu-PSMA-617 and SBRT, which could be a powerful approach against advanced prostate cancer. ^{2 3 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ... This radioligand therapy has been associated with encouraging biochemical and radiographic response rates, reduced pain, and low toxicity in multiple early- ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40752988/

Outcomes for [ 177 Lu]Lu-PSMA-617 with and Without ... This study aimed to assess the efficacy of [177Lu]Lu-PSMA-617 in patients with and without the concurrent use of an ARPI. Methods: We analyzed ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251923

Outcomes of [177Lu] Lu-PSMA-617 Re-Treatment in ... Conclusions: In our cohort, retreatment with [177Lu] Lu-PSMA-617 RLT resulted in a significant PSA response and demonstrated encouraging ...

4. novartis.com novartis.com/news/media-releases/psmaddition-data-show-novartis-pluvictotm-delays-progression-end-stage-prostate-cancer

PSMAddition data show Novartis Pluvicto™ delays ... PluvictoTM plus standard of care (ARPI + ADT) significantly reduced risk of progression or death by 28% (HR 0.72) versus SoC alone, ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00852-X/fulltext

Final overall survival and safety analyses of the phase III ... At the time of the final OS analysis, 299 deaths were reported in 142/234 participants (60.7%) in the 177Lu-PSMA-617 arm and 157/234 (67.1%) in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12481865/

Adverse events associated with Lutetium-177-PSMA-617 ... Pluvicto® can bind to prostate cancer cells expressing prostate-specific membrane antigen and induce DNA damage through the radiation ...

7. novartis.com novartis.com/us-en/news/media-releases/psmaddition-data-show-novartis-pluvictotm-delays-progression-end-stage-prostate-cancer

PSMAddition data show Novartis Pluvicto™ delays ... PluvictoTM plus standard of care (ARPI + ADT) significantly reduced risk of progression or death by 28% (HR 0.72) versus SoC alone, ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0302283823032979

Safety Analyses of the Phase 3 VISION Trial of [177Lu]Lu- ... 177 Lu-PSMA-617 plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone.