Radioligand Therapy for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+8 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Novartis Pharmaceuticals

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

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

No Placebo Group

Approved in 2 Jurisdictions

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}

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.

Trial 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 (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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Nebraska Cancer Specialists Omaha, NE

Memorial Sloan Kettering Cancer Ctr New York, NY

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals Lead Sponsor

References

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

[New tracers and combinations in radioligand therapy for prostate cancer]. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND"> 177Lutetium radioligand therapy directed against the prostate-specific membrane antigen (PSMA) is a new approved option for the treatment of metastatic, castration-resistant prostate cancer associated with a favorable toxicity profile.

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] Radioligand therapy (RLT) with Lu-177-labeled PSMA-ligands is a new therapy option for prostate cancer. Biodistribution in normal tissues is of interest for therapy planning. We evaluated if the biodistribution of Ga-68-PSMA-11 is influenced by tumor load.

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] 177Lu-DOTAGA-(l-y)fk(Sub-KuE) a.k.a. 177Lu-PSMA I&T is currently used for radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) in several centers in Europe.

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

[PSMA-targeted radioligand therapy in prostate cancer]. [2021] Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany. Several retrospective case series demonstrate its activity with a prostate-specific antigen (PSA) decrease >50% in 30-60% of mCRPC patients. The toxicity seems to be low. Hematologic grade 4 toxicity has not been observed and grade 3 toxicities rarely occur. The main nonhematologic adverse events are intermittent dry mouth because of unspecific PSMA expression in the salivary glands as well as fatigue and nausea. Currently there are no prospective studies available for evaluation of PSMA-targeted RLT and a survival benefit over approved standard therapies such as abiraterone, enzalutamide, radium-223-dichloride, docetaxel or cabazitaxel has not been shown. PSMA-targeted RLT should therefore currently only be offered after critical evaluation in patients who exhausted the approved standard therapies.

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

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021] Systemic radionuclide therapy with 177Lu-PSMA-617 is a novel treatment option in patients with metastasized and castration-resistant prostate cancer 4. The molecular target of the 177Lu-PSMA-617 radioligand therapy is the prostate-specific membrane antigen (PSMA) highly expressed on prostate cancer cells. Beyond the enhanced accumulation of PSMA on prostate cancer cells, PSMA expression is also found on the molecular surface or in the tumor-associated neovasculature of various tumor tissues including sarcomas of the soft tissue 2. Thus, PSMA has theoretically been discussed as a possible future target for systemic radioligand therapy with 177Lu-PSMA-617 even in non-prostate malignancies 1.Here we report on a female patient with extended metastasized leiomyosarcoma experimentally treated with one application of 177Lu-PSMA-617 radioligand therapy.

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

Delayed Nephrotoxicity After 225Ac-PSMA-617 Radioligand Therapy. [2023] 177Lu-PSMA-617 radioligand therapy (RLT) has evolved as a suitable alternative to existing therapeutic options in patients with metastatic castration-resistant prostate cancer. With the emergence of α-emitters such as 225Ac, the efficacy of PSMA-RLT has further improved. Xerostomia and myelosuppression are common early treatment-emergent adverse events in patients receiving this therapy; however, data on long-term toxicity are relatively scarce. In this report, we describe a 76-year-old man with metastatic castration-resistant prostate cancer, who after having an initial excellent response to 2 cycles of 225Ac-PSMA-617 RLT, developed delayed nephrotoxicity in the form of tubulointerstitial nephritis.

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] Radioligand therapy (RLT) with (177)Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments.

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] Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA.

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

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND">Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients.

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

177Lu-PSMA Radioligand Therapy for Prostate Cancer. [2022] 177Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using inhibitors of PSMA is a novel therapeutic option in patients with metastatic castration-resistant prostate cancer. The current literature suggests that this therapy is well tolerated and effective. On the basis of clinical need and current evidence, the therapy is being implemented in a growing number of centers worldwide. Here, we review important aspects of 177Lu-PSMA RLT, including patient stratification, the therapy protocol, concomitant medication, and follow-up, to inform medical staff involved in the RLT and care of patients with metastatic castration-resistant prostate cancer.