Radioactive Drugs + Targeted Radiation Therapy for Prostate Cancer

(ANDROMEDA Trial)

Overseen By Christy Palodichuk

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Androgen deprivation, Chemotherapy

Disqualifiers: Neuroendocrine, Small cell carcinoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 12-16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two radioactive drugs, Actinium Ac 225 Vipivotide Tetraxetan (225Ac-PSMA-617) and Lutetium Lu 177 Vipivotide Tetraxetan (177Lu-PSMA-617), alongside stereotactic body radiotherapy (SBRT), to treat prostate cancer that has recurred and spread to a few other areas. These drugs target a protein on specific prostate cancer cells and release radiation to destroy them. The trial aims to determine if these treatments can effectively manage recurrent and oligometastatic prostate cancer. Individuals with prostate cancer that has spread to 1-5 areas outside the prostate and who are asymptomatic might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy or cytotoxic chemotherapy, you must have stopped these treatments at least 6 months before joining the trial.

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

Research has shown that both 177Lu-PSMA-617 and 225Ac-PSMA-617 treatments for prostate cancer have undergone safety testing in people. Studies on 177Lu-PSMA-617 indicate it is generally well-tolerated, though over 30% of patients experienced a decrease in certain blood cells, like lymphocytes, which support the immune system.

For 225Ac-PSMA-617, research suggests it might be even more effective, though it can have side effects. Long-term safety studies have noted some risks, but detailed information on side effects in humans is less complete compared to 177Lu-PSMA-617.

Both treatments are in clinical trials, and their safety is still under evaluation. Being in a phase two trial suggests some early evidence of safety from previous studies. However, more research is needed to confirm the safety of these treatments for a larger group of patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a new approach to fighting prostate cancer using radioactive drugs like Actinium Ac 225 Vipivotide Tetraxetan and Lutetium Lu 177 Vipivotide Tetraxetan. Unlike standard treatments such as hormone therapy or chemotherapy, these drugs deliver targeted radiation directly to cancer cells, potentially increasing effectiveness while minimizing damage to healthy tissues. Each treatment has a unique radioactive element: Lutetium Lu 177 is known for its ability to penetrate and damage cancer cells, while Actinium Ac 225 offers a more potent, shorter-range radiation, which could be useful for aggressive cancer types. By combining these drugs with targeted radiation therapy, researchers hope to see improved outcomes and fewer side effects compared to traditional methods.

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

This trial will compare two treatments for prostate cancer: 177Lu-PSMA-617 and 225Ac-PSMA-617. Studies have shown that 177Lu-PSMA-617 can extend the lives of prostate cancer patients, with one study reporting an average survival of 15.3 months after treatment began. Additionally, about 69% of patients experienced a decrease in a cancer marker in their blood, and more than half saw a reduction of over 50%.

225Ac-PSMA-617, another treatment option in this trial, might be even more effective. It uses a type of radiation that could better kill cancer cells. Early studies indicate it is well-tolerated and shows promise in controlling tumor growth. Both treatments target a specific protein on prostate cancer cells, delivering radiation directly to them. ^{1 2 6 7 8}

Who Is on the Research Team?

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent, oligometastatic prostate cancer. Participants should have a specific protein on their tumor cells and must be suitable for precise radiation therapy to the body. Details about who can join are not fully provided.

Inclusion Criteria

Serum testosterone > 150 ng/dL

White blood cell count ≥ 2.5 × 10^9/L

Platelets ≥ 100 × 10^9/L

Exclusion Criteria

Total bilirubin > 1.5 × ULN or > 3.0 × ULN if known history of Gilbert's syndrome

Alanine aminotransferase or aspartate aminotransferase > 3 × ULN (or 5 × ULN for patients with known liver metastases)

My kidney function is low, with a GFR under 60 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 177Lu-PSMA-617 or 225Ac-PSMA-617 followed by stereotactic body radiotherapy (SBRT)

12-16 weeks

Multiple visits for radionuclide infusion and SBRT

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 3 months

Long-term follow-up

Participants are monitored for progression-free survival and other outcomes

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Actinium Ac 225 Vipivotide Tetraxetan
• Lutetium Lu 177 Vipivotide Tetraxetan
• Stereotactic Body Radiation Therapy

Trial Overview The study compares two radioactive drugs, 225Ac-PSMA-617 and 177Lu-PSMA-617, combined with targeted radiation therapy (SBRT) to treat prostate cancer that has spread but is limited in number of sites (oligometastatic).

How Is the Trial Designed?

Group I: Arm II (225Ac-PSMA-617) Experimental Treatment 5 Interventions

Patients receive 225Ac-PSMA-617 IV once. 4-6 weeks after completion of 225Ac-PSMA-617 patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT scan. Within 4 weeks of the scan, patients receive SBRT, for 1-5 treatments, over 1- 1- days. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA PET/CT scan and blood sample collection throughout the study.

Group II: Arm I (177Lu-PSMA-617) Experimental Treatment 5 Interventions

Patients receive 177Lu-PSMA-617 IV, over 1-10 minutes, on day one of each cycle. Cycles repeat every 6 weeks for 2 cycles. 4-6 weeks after completion of 177Lu-PSMA-617 patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT scan. Within 4 weeks of the scan, patients receive SBRT, for 1-5 treatments, over 1- 1- days. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA PET/CT scan and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Novartis Pharmaceuticals

Industry 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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11816130/

Long-Term Safety and Survival Outcomes of [225Ac]Ac- ... These results emphasize the potential of [225Ac]Ac-PSMA as an effective therapy for advanced prostate cancer, especially regarding long-term ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04597411

NCT04597411 | Study of 225Ac-PSMA-617 in Men With ... This is a Phase 1, open-label, international, dose escalation study to evaluate the safety of 225Ac-Ac-PSMA-617 (225Ac-PSMA-617) in men with PSMA-positive ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11900-y

Evaluation of the tolerability and safety of [225Ac]Ac-PSMA ... Life expectancy of patients with metastatic castration-resistant prostate cancer (mCRPC) is still limited despite several systemic treatments.

4. ejnmmipharmchem.springeropen.com ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-025-00344-9

[225Ac]Ac-PSMA-617 production method: development of an ... Targeted Alpha Therapy shows very promising clinical results in a cancer treatment and it should be comparable or better than chemotherapy ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/30/11/2531/745373/Preclinical-Efficacy-of-a-PSMA-Targeted-Actinium

Preclinical Efficacy of a PSMA-Targeted Actinium-225 ... Ac-pelgi shows good tolerability and clear antitumor efficacy in preclinical cell- and patient-derived xenograft prostate cancer models. Furthermore, it ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07054346

NCT07054346 | Comparison of 177Lu-PSMA-617 and ... There is evidence that Actinium-225 Prostate-Specific Membrane Antigen (225Ac-PSMA) has a potentially higher level of efficacy than 177 Lutetium ...

7. ejnmmipharmchem.springeropen.com ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-025-00333-y

Hematological toxicity of [225Ac]Ac-PSMA-617 and [177Lu]Lu ... [225Ac]Ac-PSMA-617-treated mice had a median survival of 70 days, compared to 58 days for [177Lu]Lu-PSMA-617-treated mice and 30 days for the ...

8. dailynews.ascopubs.org dailynews.ascopubs.org/do/understanding-sequential-use-radiopharmaceuticals-metastatic-castration-resistant

Understanding the Sequential Use of ... LuPSMA is generally safe regardless of prior treatment with radium-223; however, cumulative marrow toxicity may increase the risk for on-treatment cytopenias.