Radioligand Therapy for Prostate Cancer

Recruiting at 17 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: CNS metastases, Cord compression, ECG abnormalities, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 22

Duration: 36 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called radioligand therapy to assess its effects on specific markers on prostate cancer cells. It targets patients with metastatic neuroendocrine prostate cancer, meaning the cancer has spread and exhibits particular characteristics. Administered through an IV, the treatment targets specific proteins on cancer cells to determine which treatment works best based on these proteins. Suitable candidates have prostate cancer that has spread and shows neuroendocrine traits, indicated by certain test results or cancer features. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions controlling for proton-pump inhibitors (PPI) drugs among concomitant treatments, which suggests some medications might need adjustment. It's best to discuss your specific medications with the trial team.

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

Previous studies have shown that PSMA-targeted radioligand therapy (RLT) is safe and generally well-tolerated. Research indicates that patients experienced low levels of side effects, which were manageable with standard care. This treatment also demonstrated promising results in reducing pain and improving outcomes for people with advanced prostate cancer.

For SSTR2-targeted RLT, direct evidence on safety remains limited. The treatment is in an early phase of study, so its safety is still being determined. However, this type of therapy has shown potential in other types of cancer, suggesting it might be tolerable.

Regarding GRPR-targeted RLT, early studies revealed that repeated doses are generally tolerated. The most significant side effects involved the kidneys, but these were manageable. Overall, this treatment has shown encouraging results with a manageable safety profile.

These therapies are still under study, and ongoing research will provide more information about their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the radioligand therapies targeting PSMA, SSTR2, and GRPR for prostate cancer because they offer a novel approach compared to traditional treatments like hormone therapy and chemotherapy. Unlike these standard treatments, which often have systemic side effects, radioligand therapy specifically targets cancer cells by binding to receptors that are overexpressed in neuroendocrine prostate cancer (NEPC). This precision allows for direct delivery of radiation to cancer cells, potentially enhancing effectiveness and reducing damage to healthy tissue. Each targeted therapy focuses on a different receptor—PSMA, SSTR2, and GRPR—providing tailored treatment options that could improve outcomes for patients with specific tumor profiles.

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

This trial will evaluate three different radioligand therapies for prostate cancer: PSMA-targeted, SSTR2-targeted, and GRPR-targeted therapies. Research has shown that PSMA-targeted radioligand therapy, such as \[177Lu\]Lu-PSMA-617, holds promise for treating prostate cancer by significantly lowering PSA levels, which indicate prostate cancer activity, in more than half of the patients. This therapy targets cancer cells with radiation while minimizing side effects.

SSTR2-targeted therapy, another treatment arm in this trial, has shown early results indicating effective disease control and a good response rate in patients with neuroendocrine tumors, successfully managing cancer progression for many patients.

GRPR-targeted therapy, also under study in this trial, shows potential, with studies indicating it effectively targets tumors and increases survival times in early trials. These treatments aim to deliver radiation directly to cancer cells, reducing harm to healthy tissue. ^{1 2 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic neuroendocrine prostate cancer showing specific markers. They must have tumors visible on PET scans, progressing metastases without PSA increase, and certain elevated blood markers. Participants need controlled testosterone levels, recovery from previous treatments to a mild severity level, good bone marrow and organ function, and an ECOG status of 2 or less.

Inclusion Criteria

My prostate cancer has spread and shows neuroendocrine features.

My cancer shows positive on specific PET scans and my testosterone is at castrate level.

I have recovered from major side effects of my previous treatments.

Exclusion Criteria

I have not had radioligand therapy in the last 6 months.

I have had targeted radioligand therapy before.

I am currently using specific medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

3 visits (in-person) for radioligand imaging

Treatment

Participants receive up to 6 cycles of radioligand therapy targeting PSMA, SSTR2, or GRPR every 6 weeks

36 weeks

6 visits (in-person) for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

1 visit (in-person) for safety follow-up

Long-term Follow-up

Participants are followed until radiographic disease progression, death, lost to follow-up, or withdrawal of consent

Every 12 weeks for selected adverse events

What Are the Treatments Tested in This Trial?

Interventions

• PSMA, SSTR2 and GRPR Targeted Radioligand Therapy

Trial Overview The study tests the efficacy of targeted radioligand therapy (RLT) using [68Ga]Ga-PSMA-11, [68Ga]GA-DOTA-TATE, or [68Ga]Ga-NeoB based on tumor cell surface targets PSMA, SSTR2 or GRPR. It involves up to six cycles every six weeks of intravenous injections in participants with mNEPC.

How Is the Trial Designed?

Group I: SSTR2-predominant NEPC Experimental Treatment 9 Interventions

Group II: PSMA-predominant NEPC Experimental Treatment 6 Interventions

Group III: GRPR-predominant NEPC Experimental Treatment 6 Interventions

PSMA, SSTR2 and GRPR Targeted Radioligand Therapy is already approved in European Union, United States for the following indications:

Approved in European Union as [177Lu]Lu-PSMA-617 for:

• Metastatic castration-resistant prostate cancer (mCRPC)

Approved in United States as [177Lu]Lu-PSMA-617 for:

• Metastatic castration-resistant prostate cancer (mCRPC)

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a study of 135 prostate cancer patients, those with high tumor loads showed significantly reduced uptake of Ga-68-PSMA-11 in critical organs like the lacrimal and salivary glands, which could impact treatment planning for radioligand therapy (RLT).

The findings suggest that individualizing therapy protocols based on diagnostic PSMA PET imaging could enhance the efficacy and safety of Lu-177-labeled PSMA-ligand therapy, as reduced tracer uptake in dose-limiting organs may affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. Gaertner, FC., Halabi, K., Ahmadzadehfar, H., et al.[2018]

In a study of 10 patients with advanced prostate cancer, 70% experienced a significant decline in PSA levels after receiving radioligand therapy with Lu-PSMA, indicating promising efficacy in treating the disease.

The therapy was found to be safe, with no immediate side effects reported and only one patient experiencing relevant hematotoxicity seven weeks post-treatment, suggesting a low early side-effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study. Ahmadzadehfar, H., Rahbar, K., Kürpig, S., et al.[2022]

In a retrospective study of 20 patients with early-stage metastatic prostate cancer, PSMA-directed radioligand therapy (RLT) demonstrated a median progression-free survival of 12 months and an 85% rate of at least 50% prostate-specific antigen (PSA) response, indicating promising efficacy.

The treatment was generally well-tolerated, with most side effects being mild (grade 1-2), such as fatigue and dry mouth, although one patient experienced severe bone marrow toxicity after receiving 225Ac-PSMA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study. Banda, A., Privé, BM., Allach, Y., et al.[2023]

177Lu-PSMA radioligand therapy (RLT) is a promising treatment for patients with metastatic castration-resistant prostate cancer, showing good tolerance and effectiveness based on current literature.

The therapy is being increasingly adopted in medical centers worldwide, highlighting its growing importance in the management of this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA Radioligand Therapy for Prostate Cancer. Fendler, WP., Rahbar, K., Herrmann, K., et al.[2022]

177Lu-PSMA-617 is a promising new treatment for patients with advanced prostate cancer, specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells.

The therapy was also experimentally applied to a female patient with metastasized leiomyosarcoma, suggesting potential for PSMA-targeted treatment in other types of tumors beyond prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. Jüptner, M., Marx, M., Zuhayra, M., et al.[2021]

177Lutetium radioligand therapy is an effective treatment for metastatic, castration-resistant prostate cancer, showing a favorable safety profile, making it a valuable option for patients.

Ongoing research is exploring the use of this therapy in earlier stages of prostate cancer, as well as the development of new ligands and isotopes, which could enhance treatment efficacy and minimize side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New tracers and combinations in radioligand therapy for prostate cancer]. Tauber, R., Lunger, L., Eiber, M., et al.[2023]

Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) shows promising efficacy in treating metastatic castration-resistant prostate cancer (mCRPC), with a prostate-specific antigen (PSA) decrease of over 50% observed in 30-60% of patients based on several retrospective case series.

The treatment appears to have low toxicity, with no reported grade 4 hematologic toxicities and only rare occurrences of grade 3 toxicities, although patients may experience mild nonhematologic side effects like dry mouth, fatigue, and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[PSMA-targeted radioligand therapy in prostate cancer]. Heck, MM., Retz, M., Tauber, R., et al.[2021]

In a study of 71 patients with metastatic castration-resistant prostate cancer, 56% experienced a significant PSA decline of 50% or more after receiving three cycles of Lutetium-177 labeled PSMA-617 radioligand therapy, indicating its efficacy as a treatment option.

The therapy demonstrated delayed responses, as 28 out of 30 patients who responded after the first cycle continued to show positive results, and 12 out of 41 initial non-responders responded to subsequent cycles, highlighting the potential for ongoing therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. Rahbar, K., Bögeman, M., Yordanova, A., et al.[2021]

In a patient with metastatic castration-resistant prostate cancer (mCRPC), four cycles of radioligand therapy (RLT) using 177Lu-PSMA I&T resulted in over 97% destruction of metastatic tumors, indicating high efficacy of this treatment.

The study highlights the need for individualized dosimetry to account for variations in tumor response and suggests that measuring 177Lu-PSMA activity concentrations could improve routine dosimetry practices, while also noting that the first cycle of RLT has the most significant impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. Kelk, E., Ruuge, P., Rohtla, K., et al.[2021]

177Lu-PSMA-617 radioligand therapy (RLT) is an effective treatment for patients with metastatic castration-resistant prostate cancer, and the use of α-emitters like 225Ac has further enhanced its efficacy.

While initial responses to 225Ac-PSMA-617 RLT can be excellent, there is a risk of delayed nephrotoxicity, as demonstrated by a case of tubulointerstitial nephritis in a 76-year-old patient, highlighting the need for monitoring long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy. Satapathy, S., Sharma, A., Sood, A., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06379217

NCT06379217 | NEPC Study: An Exploratory Safety and ... The purpose of this study is to evaluate the change in the expression of treatment targets on the surface of tumor cells (Prostate Specific Membrane Antigen ...

2. novartis.com novartis.com/clinicaltrials/study/nct06379217

NEPC Study: An Exploratory Safety and Efficacy ... The purpose of this study is to evaluate the change in the expression of treatment targets on the surface of tumor cells (Prostate Specific Membrane Antigen ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10828073/

The Balance Between the Therapeutic Efficacy and Safety ... Treatment of PC-3 tumors with all three studied [177Lu]Lu-NeoB doses was effective. Median survival times were significantly (p < 0.0001) ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0001299825000911

GRPR Expression in Metastatic Cancers: A Review of ... Preclinical and early clinical studies demonstrate encouraging tumor targeting and therapeutic efficacy with manageable toxicity profiles, ...

5. pubs.acs.org pubs.acs.org/doi/full/10.1021/acsptsci.5c00491

Preclinical Evaluation of a 177 Lu-Labeled Gastrin-Releasing ... [177Lu]Lu-LF1 shows promise as a therapeutic radioligand for GRPR-positive prostate cancer, offering high tumor uptake and rapid clearance from ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9605926/

Safety of [177Lu]Lu-NeoB treatment: a preclinical study ... In general, repeated administration of [ 177 Lu]Lu-NeoB was tolerated. The most significant radiotoxic effects were found in the kidneys.

7. trialx.com trialx.com/clinical-trials/listings/296406/nepc-study-an-exploratory-safety-and-efficacy-study-with-psma-sstr2-and-grpr-targeted-radioligand-therapy-in-metastatic-neuroendocrine-prostate-cancer/

An Exploratory Safety and Efficacy Study ... NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer.