[225Ac]Ac-FL-020 for Prostate Cancer

(ProTACT Trial)

Recruiting at 7 trial locations

Overseen By Full-Life Technologies GmbH

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Full-Life Technologies GmbH

Must be taking: LHRH analogue

Must not be taking: Radionuclide therapy

Disqualifiers: Brain metastases, Cystitis, others

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

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called [225Ac]Ac-FL-020 for prostate cancer that has spread and is resistant to standard hormone therapy. The main goals are to assess the treatment's safety, effectiveness, and how the body processes it. Suitable participants have prostate cancer unresponsive to castration treatment, evidence of disease spreading, and have undergone previous treatments like hormone therapy or taxane chemotherapy. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had any systemic anti-cancer therapy within 6 weeks before starting the trial, except for stable bisphosphonate or denosumab regimens.

Is there any evidence suggesting that [225Ac]Ac-FL-020 is likely to be safe for humans?

A previous study found the treatment [225Ac]Ac-FL-020 to be relatively safe for patients with prostate cancer. The most common side effect, dry mouth, affected about 77.1% of patients, with only 3% experiencing it severely. Other side effects were mild and manageable.

As this trial is in its early phase, the main goal is to assess safety. Researchers are still studying how well people tolerate this treatment. However, findings so far suggest that it is generally well-tolerated in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about [225Ac]Ac-FL-020 for prostate cancer because it introduces a novel approach by using targeted alpha therapy. Unlike standard treatments like hormone therapy, chemotherapy, or radiation, this drug uses actinium-225, a radioactive substance, to deliver targeted radiation directly to cancer cells. This method aims to maximize the destruction of cancer cells while minimizing damage to surrounding healthy tissues. Additionally, its administration includes dosimetry with [111In]In-FL-020, which helps optimize the treatment plan by accurately measuring radiation doses received by the tumor. This precision and targeted action bring hope for increased effectiveness and reduced side effects compared to traditional therapies.

What evidence suggests that [225Ac]Ac-FL-020 might be an effective treatment for prostate cancer?

Research has shown that treatments like \[225Ac\]Ac-FL-020, including \[225Ac\]Ac-PSMA, have been very effective for prostate cancer. Specifically, a review of six studies involving 201 patients found that \[225Ac\]Ac-PSMA-617 effectively treated advanced prostate cancer unresponsive to hormone therapy. In this trial, researchers are studying \[225Ac\]Ac-FL-020, and some patients in early studies have shown signs of the treatment fighting cancer cells. The FDA has granted \[225Ac\]Ac-FL-020 fast-track status, indicating significant promise. While more research is needed, these early results suggest \[225Ac\]Ac-FL-020 could be a valuable option for those with advanced prostate cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Full-Life Technologies GmbH

Principal Investigator

Full-Life Technologies GmbH

Are You a Good Fit for This Trial?

This trial is for adults with metastatic castration-resistant prostate cancer (mCRPC) who have confirmed disease progression. Participants must have had prior treatments, including up to two taxane regimens and hormone therapies like abiraterone or enzalutamide. They should be in good physical condition (ECOG 0-1), have low testosterone levels maintained by medication or surgery, and show positive lesions on a PSMA-PET/CT scan.

Inclusion Criteria

My cancer has gotten worse according to my doctor.

My prostate cancer has spread and was confirmed by a lab test.

I have signed the consent form and can follow the study rules.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of [225Ac]Ac-FL-020 to determine the maximum tolerated dose

4 weeks

Weekly visits for dose administration and monitoring

Cohort Expansion

Participants receive the determined dose of [225Ac]Ac-FL-020 to further evaluate safety and efficacy

28 days

Weekly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular imaging assessments and PSA level checks

What Are the Treatments Tested in This Trial?

Interventions

• [225Ac]Ac-FL-020

Trial Overview The study tests the safety and effectiveness of [225Ac]Ac-FL-020, a radioactive therapeutic agent for mCRPC. It also examines how the body processes this drug using blood and urine samples, alongside imaging techniques like SPECT/CT scans to monitor its distribution and effects within the body.

How Is the Trial Designed?

Group I: [225Ac]Ac-FL-020 Experimental Treatment 5 Interventions

Treatment with \[225Ac\]Ac-FL-020 administered intravenously. 10 patients will also receive \[111In\]In-FL-020 for dosimetry purposes.

Who Is Running the Clinical Trial?

Full-Life Technologies GmbH

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

In a meta-analysis of 6 studies involving 201 patients with metastatic castration-resistant prostate cancer, 225Ac-PSMA-617 demonstrated a high efficacy, with 87% of patients showing any decrease in prostate-specific antigen (PSA) levels and 66% achieving a PSA decrease of more than 50%.

The treatment was found to be relatively safe, with the most common side effect being xerostomia (dry mouth) occurring in 77.1% of patients, but only 3% experiencing severe cases, indicating that 225Ac-PSMA-617 is a promising option with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. Ma, J., Li, L., Liao, T., et al.[2022]

In a preliminary study of 21 patients with de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) who refused standard treatments, 225Ac-PSMA-617 showed a significant anti-tumor effect, with 95% of patients experiencing a decline in prostate-specific antigen (PSA) levels, and 86% achieving a decline of 50% or more.

The treatment was well tolerated, with the most common side effect being mild dry mouth in 94% of patients, suggesting that 225Ac-PSMA-617 could be a promising alternative therapy for mHSPC patients who decline standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings. Sathekge, M., Bruchertseifer, F., Vorster, M., et al.[2023]

In a study of 94 patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with radium-223 ([223Ra]RaCl2) after abiraterone acetate (AA) was found to be safe, with only a 2.1% fracture rate and minimal severe side effects.

The median overall survival after starting [223Ra]RaCl2 was over 14 months, indicating that this treatment is both effective and well-tolerated in patients progressing after AA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fracture risk and survival outcomes in metastatic castration-resistant prostate cancer patients sequentially treated with abiraterone acetate and RADIUM-223. Caffo, O., Frantellizzi, V., Tucci, M., et al.[2021]

In a study of 150 men with metastatic castration-resistant prostate cancer treated with radium-223, the median overall survival was 14.5 months, highlighting its efficacy in improving survival for patients with bone metastases.

Key pre-treatment factors such as low albumin, high alkaline phosphatase, poor performance status, and high prostate-specific antigen levels were identified as predictors of poor survival, allowing for the development of a prognostic model to better select patients who may benefit from radium-223 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic factors that influence prognosis and survival outcomes in men with metastatic castration-resistant prostate cancer treated with Radium-223. Al-Ezzi, EM., Alqaisi, HA., Iafolla, MAJ., et al.[2022]

In a study of 134 men with metastatic castration-resistant prostate cancer treated with Radium-223, about 20% experienced PSA flares, but these flares did not negatively impact overall survival, which was similar to those who had PSA responses or non-responses.

The median overall survival for patients experiencing PSA flares was 16.8 months, indicating that PSA response patterns may not be reliable indicators of treatment outcomes with Radium-223, suggesting a need for further research into better markers of response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Prognostic Implications of PSA Flares during Radium-223 Treatment among Men with Metastatic Castration Resistant Prostate Cancer. Sidhu, A., Khan, N., Phillips, C., et al.[2023]

The study presents an optimized protocol for preparing Ac-225 labeled with PSMA-617, achieving a high yield of 85%-87% and radiochemical purity of 97%-99%, which is crucial for effective targeted alpha therapy in prostate cancer.

This method allows for a single-step, routine in-house radiolabeling process, making it a practical approach for delivering targeted treatment to patients with metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma. Thakral, P., Simecek, J., Marx, S., et al.[2022]

In the ALSYMPCA trial involving 600 patients treated with radium-223, the treatment was found to be well tolerated with a low incidence of myelosuppression and no new safety concerns reported up to 3 years after the first injection.

While 94% of radium-223 patients experienced treatment-emergent adverse events, serious hematologic issues were rare, and long-term follow-up showed no cases of acute myelogenous leukemia or myelodysplastic syndrome, indicating a favorable safety profile for radium-223 in treating symptomatic prostate cancer with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. Parker, CC., Coleman, RE., Sartor, O., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12388893/

Exploring the Clinical Insights into [225Ac]Ac-PSMA and Its ... Data from compassionate-use programs and small clinical trials demonstrate that [225Ac]Ac-PSMA produces significant biochemical and imaging ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS5117

A first-in-human, phase 1 dose escalation and expansion ... This Phase 1 study evaluates the safety, tolerability, and anti-tumor activity of [225Ac]Ac-FL-020 in patients with mCRPC. Methods: This first- ...

3. withpower.com withpower.com/trial/phase-1-metastatic-castration-resistant-prostate-cancer-6-2024-82609

[225Ac]Ac-FL-020 for Prostate Cancer (ProTACT Trial) In a meta-analysis of 6 studies involving 201 patients with metastatic castration-resistant prostate cancer, 225Ac-PSMA-617 demonstrated a high efficacy, with ...

4. targetedonc.com targetedonc.com/view/fda-fast-tracks-225ac-fl-020-in-mcrpc

FDA Fast Tracks 225Ac-FL-020 in mCRPC Full-Life Technologies granted FDA fast track designation for 225Ac-FL-020 for the treatment of metastatic castration-resistant prostate cancer.

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

Long-Term Safety and Survival Outcomes of [225Ac]Ac- ... This study investigates the safety of Radioligand Therapy with [225Ac]Ac-PSMA in patients with metastatic castration-resistant prostate ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2024-10276

Study With [225Ac]Ac-FL-020 in mCRPC Participants - NCI The purpose of this study is to evaluate the safety, therapeutic effect, and pharmacokinetics of [225Ac]Ac-FL-020 in participants with metastatic ...

7. uvahealth.com uvahealth.com/clinical-trials/trial/302635

Clinical Trials | A First-in-human, Phase 1 Dose Escalation ... The purpose of the study is to learn about the effects of the investigational medicinal product, called [225Ac]Ac-FL-020, to see how safe [225Ac]Ac-FL-020 is ...