What is the mechanism of action of this treatment?

177Lu-PSMA-617 is a targeted radioligand therapy that binds to Prostate-Specific Membrane Antigen (PSMA) on prostate cancer cells, delivering radioactive Lutetium-177 to destroy them. This targeted approach minimizes damage to surrounding healthy tissues, enhancing treatment efficacy and reducing side effects. Other common treatments include Androgen Deprivation Therapy (ADT), which lowers androgen levels to slow cancer growth, and chemotherapy, which kills rapidly dividing cells. Targeted therapies like 177Lu-PSMA-617 are crucial as they offer a more precise attack on cancer cells, potentially improving outcomes and quality of life for prostate cancer patients.

What side effects are associated with this type of intervention?

Common treatments for prostate cancer, particularly those involving radioligand therapy like 177Lu-PSMA-617, often have side effects such as fatigue, nausea, anemia, and thrombocytopenia. Other potential adverse reactions include elevated transaminases, anorexia, rash, constipation, vomiting, and diarrhea. Additionally, there is a risk of myelodysplastic syndrome and acute myeloid leukemia, especially in patients heavily pretreated with other therapies. Bone metastasis treatments may also lead to an increased risk of fractures, which can be mitigated by the use of osteoclast inhibitors.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that are similar to 177Lu-PSMA-617, which targets PSMA on prostate cancer cells and delivers radioactive Lutetium-177 to destroy them. One notable approval is for Radium-223 (Ra-223), an alpha-emitting radiopharmaceutical used to treat men with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases. Ra-223 has been shown to improve overall survival and delay the time to first symptomatic skeletal-related event. Additionally, other treatments like enzalutamide and abiraterone, which are androgen receptor inhibitors, have been approved for CRPC. These treatments, while not radiopharmaceuticals, are often part of the standard of care in combination with radiopharmaceuticals like Ra-223.

What other types of research exist?

Promising novel alternatives to 177Lu-PSMA-617 for prostate cancer treatment in 2024 include: 1) Ra-223 (Radium-223), an alpha particle-emitting agent that prolongs overall survival and decreases symptomatic skeletal events in metastatic castration-resistant prostate cancer (CRPC). 2) Beta-emitting radioisotopes like Strontium-89 and Samarium-153, which have been used for pain palliation in bone metastases. 3) Immunotherapy approaches such as CAR-T cells targeting PSMA (e.g., P-PSMA-101 CAR-T cells) are in early-phase trials and show potential. 4) Combination therapies involving systemic agents like abiraterone, enzalutamide, and docetaxel, which have shown improved outcomes in various studies. These alternatives are under investigation and may offer new avenues for treatment.

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Radioisotope Therapy

177Lu-PSMA-617 + Standard Therapy for Prostate Cancer (PSMAddition Trial)

Phase 3

Waitlist Available

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

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

Must have

Patients must be adults ≥18 years of age

Patients must have an ECOG performance status of 0 to 2

Must not have

Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed

Concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy or investigational therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of randomization until date of death from any cause, assessed up to 50 months (estimated final os analysis)

Awards & highlights

Summary

This trial is testing a new cancer treatment in men with mHSPC. The new treatment is given with the standard of care, which is a combination of two existing treatments. 1126 patients will be randomly assigned to either the new treatment or the standard of care.

Who is the study for?

Adult men with metastatic hormone-sensitive prostate cancer, who have visible bone or soft tissue/visceral lesions and are either treatment-naive or minimally treated. They must be over 18 years old, have a life expectancy of more than 9 months, good organ function, no severe concurrent conditions, and not be on other clinical trials.Check my eligibility

What is being tested?

The trial is testing the effectiveness and safety of adding a drug called 177Lu-PSMA-617 to the standard prostate cancer treatments (Androgen Receptor Directed Therapy + Androgen Deprivation Therapy) compared to the standard treatments alone in about 1126 patients.See study design

What are the potential side effects?

Potential side effects include reactions related to radiation exposure from radioligand therapy like nausea, fatigue, blood cell count changes that can affect immunity and clotting. Organ-specific toxicity such as kidney damage may also occur.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I can take care of myself and am up and about more than half of my waking hours.

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I have prostate cancer that has spread, confirmed by a biopsy.

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I have metastatic prostate cancer and am expected to live more than 9 months.

Exclusion Criteria

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

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I haven't had specific radiation treatments or PSMA-targeted therapy in the last 6 months.

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I am not currently on any strong cancer treatments like chemotherapy.

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I cannot raise my arms.

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My cancer is growing quickly and needs immediate treatment with taxane-based chemotherapy.

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I have not received a transfusion just to qualify for this study.

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I am experiencing symptoms or have been diagnosed with potential spinal cord compression.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization until date of death from any cause, assessed up to 50 months (estimated final os analysis)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization until date of death from any cause, assessed up to 50 months (estimated final os analysis)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until date of death from any cause, assessed up to 50 months (estimated final os analysis) for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Radiographic Progression Free Survival (rPFS)

Secondary outcome measures

Brief Pain Inventory-short Form (PBI-SF)

Change in nadir level of PSA lower than 0.2 ng/ml

Disease Control Rate (DCR)

+13 more

Side effects data

From 2023 Phase 3 trial • 831 Patients • NCT03511664

43%

Fatigue

39%

Dry mouth

35%

Nausea

30%

Anaemia

23%

Back pain

22%

Arthralgia

21%

Decreased appetite

19%

Constipation

19%

Diarrhoea

18%

Vomiting

17%

Thrombocytopenia

14%

Lymphopenia

12%

Leukopenia

11%

Weight decreased

10%

Urinary tract infection

10%

Bone pain

Oedema peripheral

Dyspnoea

Neutropenia

Pain in extremity

Cough

Dizziness

Hypocalcaemia

Haematuria

Fall

Hypokalaemia

Headache

Hypertension

Pyrexia

Asthenia

Pain

Abdominal pain

Blood creatinine increased

Hypophosphataemia

Insomnia

Sepsis

Acute kidney injury

Mental status changes

Urinary tract obstruction

Urinary retention

Infection

Urosepsis

Deep vein thrombosis

Dehydration

Pancytopenia

Hypotension

Ischaemic stroke

Pulmonary embolism

Spinal cord compression

Syncope

Subdural haematoma

Pneumonia

100%

80%

60%

40%

20%

Study treatment Arm

177Lu-PSMA-617 Plus Best Supportive/Best Standard of Care (BS/BSOC)

Best Supportive/Best Standard of Care (BS/BSOC) Alone

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: 177Lu-PSMA-617Experimental Treatment4 Interventions

Participant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA-617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

Group II: Standard of CareActive Control3 Interventions

For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

177Lu-PSMA-617

2018

Completed Phase 3

~840

68Ga-PSMA-11

2019

Completed Phase 3

~170

ADT

2009

Completed Phase 3

~5120

0 / 10Eligibility 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

177Lu-PSMA-617 is a targeted radioligand therapy that binds to Prostate-Specific Membrane Antigen (PSMA) on prostate cancer cells, delivering radioactive Lutetium-177 to destroy them. This targeted approach minimizes damage to surrounding healthy tissues, enhancing treatment efficacy and reducing side effects. Other common treatments include Androgen Deprivation Therapy (ADT), which lowers androgen levels to slow cancer growth, and chemotherapy, which kills rapidly dividing cells. Targeted therapies like 177Lu-PSMA-617 are crucial as they offer a more precise attack on cancer cells, potentially improving outcomes and quality of life for prostate cancer patients.