Radioligand Therapy for Prostate Cancer

Recruiting at 9 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

Trial Summary

What is the purpose of this trial?

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 (PSMA), Somatostatin Receptor 2 (SSTR2), and Gastrin Releasing Peptide Receptor (GRPR) between the start and after the completion of radioligand therapy (RLT). Study will use radioligand imaging (RLI) to determine predominantly expressed target on the surface of tumor cells. Based on predominant expression of target, corresponding RLT targeting PSMA, SSTR2, or GRPR RLT will be given for up to 6 cycles every 6 weeks as intravenous (i.v.) injection in participants with metastatic neuroendocrine prostate cancer (mNEPC).

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.

What data supports the effectiveness of the treatment for prostate cancer?

The treatment using 177Lu-PSMA-617 has shown effectiveness in prostate cancer by reducing prostate-specific antigen (PSA) levels by more than 50% in 30-60% of patients with advanced prostate cancer, with low toxicity. This suggests it can be a promising option for patients who have exhausted other standard therapies. ^{1 2 3 4 5}

Is radioligand therapy for prostate cancer generally safe for humans?

Radioligand therapy for prostate cancer, such as PSMA-targeted treatments, generally has a favorable safety profile. Common side effects include dry mouth and fatigue, while serious blood-related side effects are rare. However, there are reports of delayed kidney issues in some patients. ^{1 4 6 7 8}

What makes PSMA, SSTR2, and GRPR Targeted Radioligand Therapy unique for prostate cancer treatment?

This treatment is unique because it uses radioligands (radioactive substances) that specifically target proteins like PSMA, SSTR2, and GRPR found on prostate cancer cells, allowing for precise delivery of radiation to the cancer cells while sparing normal tissues. This targeted approach is novel compared to traditional therapies and is being explored for its effectiveness in both hormone-sensitive and castration-resistant prostate cancer. ^{2 5 7 9 10}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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 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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[New tracers and combinations in radioligand therapy for prostate cancer]. [2023]

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

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. [2018]

3. Switzerland 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. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[PSMA-targeted radioligand therapy in prostate cancer]. [2021]

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

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021]

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

Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy. [2023]

7. Germany 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. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study. [2023]

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

177Lu-PSMA Radioligand Therapy for Prostate Cancer. [2022]