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

Recruiting at 3 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

Trial Summary

What data supports the effectiveness of the treatment [225Ac]Ac-FL-020 for prostate cancer?

Research on a similar treatment, 225Ac-PSMA-617, shows it has a good anti-tumor effect in patients with metastatic prostate cancer, suggesting potential effectiveness for [225Ac]Ac-FL-020 as well. ^{1 2 3 4 5}

How is the drug [225Ac]Ac-FL-020 different from other prostate cancer treatments?

[225Ac]Ac-FL-020 is unique because it uses a radioactive substance called Actinium-225 to target and kill prostate cancer cells specifically, which is different from traditional treatments that may not be as targeted. This approach, known as targeted alpha therapy, aims to minimize damage to healthy cells while effectively treating cancer. ^{3 4 5 6 7}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, therapeutic effect, and pharmacokinetics of \[225Ac\]Ac-FL-020 in participants with metastatic castration-resistant prostate cancer (mCRPC).

Research Team

Full-Life Technologies GmbH

Principal Investigator

Full-Life Technologies GmbH

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence and Prognostic Implications of PSA Flares during Radium-223 Treatment among Men with Metastatic Castration Resistant Prostate Cancer. [2023]

2. United States 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. [2022]

3. Switzerland 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. [2022]

4. Switzerland 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. [2022]

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

225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings. [2023]

6. India 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. [2022]

7. Germany 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. [2021]