What is the mechanism of action of this treatment?

Radioligand therapy, such as 177Lu-PSMA-I&T, targets the Prostate-Specific Membrane Antigen (PSMA) on prostate cancer cells, delivering radioactive particles directly to the tumor, thereby minimizing damage to surrounding healthy tissue. Hormone therapy reduces androgen levels or blocks their effects, slowing the growth of cancer cells that rely on these hormones. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cancer cells, while immunotherapy stimulates the patient's immune system to recognize and attack cancer cells. These treatments are crucial as they offer targeted, systemic, or immune-based approaches to manage and potentially reduce prostate cancer progression, improving patient outcomes and quality of life.

What side effects are associated with this type of intervention?

Radioligand therapy targeting PSMA, such as 177Lu-PSMA-I&T, is associated with several side effects. Common adverse events include myelosuppression (e.g., thrombocytopenia, lymphopenia, anemia, leukopenia), nephrotoxicity, and salivary gland toxicity (e.g., pain, swelling, dry mouth). Nausea is also frequently reported, often due to the amino acid infusions used to protect the kidneys during therapy. These side effects are generally mild to moderate, but serious adverse events can occur, particularly high-grade bone marrow suppression.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer, including radioligand therapies targeting PSMA. One notable approval is for lutetium Lu 177 vipivotide tetraxetan, which has shown significant efficacy in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). This treatment demonstrated improved progression-free survival and overall survival in clinical trials. Additionally, other treatments such as androgen receptor signaling inhibitors (e.g., enzalutamide, apalutamide, darolutamide) and taxane-based chemotherapies (e.g., docetaxel, cabazitaxel) have been approved for various stages of prostate cancer, providing a range of therapeutic options.

What other types of research exist?

Promising alternatives to 177Lu-PSMA-I&T for prostate cancer treatment include: 1) Ra-223 (Radium-223), an alpha particle-emitting agent that prolongs overall survival and decreases symptomatic skeletal-related events (SREs) in metastatic castration-resistant prostate cancer (mCRPC). 2) Next-generation imaging techniques like Ga-68 PSMA-11 PET/CT and PET/MRI, which can improve detection and staging of prostate cancer, potentially leading to more tailored and effective treatment strategies. 3) Combination therapies such as Ra-223 with docetaxel, which have shown improved outcomes in clinical trials. 4) Systemic therapies like abiraterone/prednisone and enzalutamide, which are effective in reducing SREs and improving quality of life in mCRPC patients.

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Radioisotope Therapy

177Lu-PSMA-I&T for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Radioligand therapy, such as 177Lu-PSMA-I&#x26;T, targets the Prostate-Specific Membrane Antigen (PSMA) on prostate cancer cells, delivering radioactive particles directly to the tumor, thereby minimizing damage to surrounding healthy tissue. Hormone therapy reduces androgen levels or blocks their effects, slowing the growth of cancer cells that rely on these hormones. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cancer cells, while immunotherapy stimulates the patient's immune system to recognize and attack cancer cells. These treatments are crucial as they offer targeted, systemic, or immune-based approaches to manage and potentially reduce prostate cancer progression, improving patient outcomes and quality of life.

Q: What side effects are associated with this type of intervention?

Radioligand therapy targeting PSMA, such as 177Lu-PSMA-I&#x26;T, is associated with several side effects. Common adverse events include myelosuppression (e.g., thrombocytopenia, lymphopenia, anemia, leukopenia), nephrotoxicity, and salivary gland toxicity (e.g., pain, swelling, dry mouth). Nausea is also frequently reported, often due to the amino acid infusions used to protect the kidneys during therapy. These side effects are generally mild to moderate, but serious adverse events can occur, particularly high-grade bone marrow suppression.

Q: What other types of research exist?

Promising alternatives to 177Lu-PSMA-I&#x26;T for prostate cancer treatment include: 1) Ra-223 (Radium-223), an alpha particle-emitting agent that prolongs overall survival and decreases symptomatic skeletal-related events (SREs) in metastatic castration-resistant prostate cancer (mCRPC). 2) Next-generation imaging techniques like Ga-68 PSMA-11 PET/CT and PET/MRI, which can improve detection and staging of prostate cancer, potentially leading to more tailored and effective treatment strategies. 3) Combination therapies such as Ra-223 with docetaxel, which have shown improved outcomes in clinical trials. 4) Systemic therapies like abiraterone/prednisone and enzalutamide, which are effective in reducing SREs and improving quality of life in mCRPC patients.

Phase 3

Waitlist Available

Research Sponsored by Curium US LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Progressive disease by one or more of the following criteria: Serum/plasma PSA progression, Progression of measurable disease or presence of at least two new bone lesions

Effective castration with serum testosterone level of <50 ng/dL

Must not have

Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2

Patients with known HRR gene-mutation who have not been previously treated with olaparib or rucaparib

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 156 weeks

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new radioactive drug against standard hormone therapy in men with advanced prostate cancer that doesn't respond to usual treatments. The drug targets and kills cancer cells using radiation. The drug being tested, 225Ac-PSMA-617, has shown promise in inducing complete responses in patients with metastatic castrate-resistant prostate cancer who were resistant to standard therapies.

Who is the study for?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy can join. They must have tried and progressed on treatments like abiraterone or enzalutamide, but not more than one type. A positive PSMA-PET scan is needed, and they should be effectively castrated with low testosterone levels. HIV or hepatitis B/C patients may qualify if well-managed. Participants need a life expectancy of at least 6 months and agree to use contraception.

What is being tested?

This study compares the safety and effectiveness of a new treatment called 177Lu-PSMA-I&T against standard hormone therapies (abiraterone with prednisone or enzalutamide) in men whose prostate cancer has spread despite castration. It's an open-label trial where everyone knows which treatment they're getting, and it randomly assigns participants to either group.

What are the potential side effects?

Possible side effects for the new treatment include nausea, fatigue, dry mouth, changes in blood counts leading to increased risk of infection or bleeding, kidney damage, and temporary pain flare-ups in areas where cancer has spread.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer has worsened, shown by rising PSA levels, growth of tumors, or new bone lesions.

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My testosterone levels are below 50 ng/dL due to treatment.

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I have received ARAT for my cancer and it has progressed despite the treatment.

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My prostate cancer is confirmed without a major small cell component.

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I am willing to start ARAT therapy.

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I have been treated with advanced hormone therapy for cancer.

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I have had only one previous hormone therapy for cancer.

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I am a man over 18 and can sign a consent form.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My physical functioning is somewhat limited.

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I have an HRR gene mutation and haven't been treated with olaparib or rucaparib.

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My organ and bone marrow functions are not meeting certain health standards.

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I am not currently receiving any other cancer treatments.

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I have been on a stable dose of zoledronic acid for bone therapy for at least 4 weeks.

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I have cancer, but it's not low-grade bladder cancer or non-melanoma skin cancer.

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I have not had radium-223 treatment in the last 3 months.

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I haven't used any experimental drugs in the last 4 weeks.

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I have a serious heart condition.

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I have used G-CSF for ongoing low white blood cell count after standard treatment.

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I have previously received treatment with radioligand therapy.

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I have symptoms or signs of potential spinal cord compression.

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I have not had major surgery in the last 30 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 156 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~156 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 156 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Radiographic Progression Free Survival

Secondary study objectives

Overall Survival (OS)

PSA50 Response Rate

Progression Free Survival

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Investigational DrugExperimental Treatment1 Intervention

177Lu-PSMA-I\&T

Group II: Standard Of Care Hormone TherapyActive Control1 Intervention

Abiraterone with Prednisone or Enzalutamide

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Radioligand therapy, such as 177Lu-PSMA-I&T, targets the Prostate-Specific Membrane Antigen (PSMA) on prostate cancer cells, delivering radioactive particles directly to the tumor, thereby minimizing damage to surrounding healthy tissue. Hormone therapy reduces androgen levels or blocks their effects, slowing the growth of cancer cells that rely on these hormones. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cancer cells, while immunotherapy stimulates the patient's immune system to recognize and attack cancer cells. These treatments are crucial as they offer targeted, systemic, or immune-based approaches to manage and potentially reduce prostate cancer progression, improving patient outcomes and quality of life.

Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review.[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study.