177Lu-HTK03170 for Prostate Cancer

Overseen By Research Manager

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: British Columbia Cancer Agency

Must be taking: Abiraterone, Enzalutamide, ARAT therapy

Must not be taking: Chemotherapy, Immunotherapy, Targeted therapy

Disqualifiers: Brain metastases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will determine the safe initial injected activity of the radioligand therapy 177Lu-HTK03170 for the measurement of dosimetry and initiation of treatment in subjects with PSMA-positive, metastatic castrate resistant prostate cancer, (mCRPC). Subjects will receive treatment which will be escalated between cycles and personalized based on dosimetry calculations and imaging. In addition, antitumour activity will be measured by radiographic response, and further assessments of the treatment will be measured by CT imaging, ctDNA/ctRNA, PSA, PSMA PET/CT, and quality of life questionnaires. Subjects will be followed for 2 years or until they have progression and are switched to another systemic treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had any systemic anti-cancer therapy within 28 days before enrollment.

What data supports the idea that 177Lu-HTK03170 for Prostate Cancer is an effective treatment?

The available research shows that 177Lu-HTK03170, also known as 177Lu-PSMA-617, is effective for treating prostate cancer, particularly in cases where the cancer is resistant to other treatments. Studies have shown that this treatment can improve outcomes for patients with advanced prostate cancer that has spread and is not responding to standard therapies. In comparisons with another treatment called docetaxel, 177Lu-PSMA-617 has shown favorable results, suggesting it is a strong alternative for patients who have not yet undergone chemotherapy. This indicates that 177Lu-HTK03170 is a promising option for those with difficult-to-treat prostate cancer. ^{1 2 3 4 5}

What safety data exists for 177Lu-HTK03170 in prostate cancer treatment?

The provided research does not specifically mention 177Lu-HTK03170, but it discusses the safety of Lutetium-177 PSMA-617, a similar radiopharmaceutical used in prostate cancer treatment. Studies indicate that Lutetium-177 PSMA-617 has been evaluated for safety in various clinical settings, including metastatic castration-resistant prostate cancer. The safety profile of Lutetium-177 based radiopharmaceuticals, like PSMA-617, is well-reported, and efforts are ongoing to optimize their risk-benefit trade-off in clinical practice. ^{1 2 3 6 7}

Is the drug 177Lu HTK03170 a promising treatment for prostate cancer?

Yes, 177Lu HTK03170 is a promising drug for prostate cancer. Similar treatments using Lutetium-177 have shown positive results in patients with advanced prostate cancer, especially for those who do not respond to standard therapies. These treatments have been effective and safe, offering a new option for patients. ^{1 3 5 8 9}

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, despite previous treatments like abiraterone or enzalutamide. They must have good blood counts, kidney and liver function, be able to follow the trial procedures, and use contraception if necessary. Excluded are those who've had recent cancer therapies or surgeries, active heart disease, other cancers, brain metastases or certain conditions affecting saliva production.

Inclusion Criteria

I am a man aged 18 or older.

Evidence of biochemical or imaging progression as defined by the study protocol

Life expectancy of > 6 months

Exclusion Criteria

I have not had major surgery in the last 4 weeks.

I have not had radiation on my cancer spots in the last 4 weeks.

I have a history of factors causing dry mouth or currently have mild to severe dry mouth.

Treatment Details

Interventions

• 177Lu HTK03170
• 68Ga-HTK03149

Trial Overview The study tests a new radioactive drug called 177Lu-HTK03170 in men with PSMA-positive mCRPC. The treatment amount will increase each cycle based on personalized calculations from imaging results. Researchers will monitor tumor response through scans and blood tests for two years or until the disease progresses.

Participant Groups

Group I: 177Lu HTK03170 Phase I/II Experimental Treatment 2 Interventions

Phase I, the administered activity will be 1.1 GBq ± 10% as an intravenous infusion over a time of 10 to 30 minutes. Initial Activity (IA) escalation will only occur on the initial dosimetry IA, with an increase of 30% over the initial IA (used for dosimetry) at each subsequent level ( 1.65 GBq, 2.5 GBq, 3.7 GBq) in up to 12 participants. Personalized dosimetry will be calculated for each subject. Phase II, subjects will be treated with an initial IA of 177Lu-HTK03170 at the MTIA as determined during Phase I or 13.7 GBq whichever is lower. Treatment is administered as an intravenous infusion over a time of 10 - 30 minutes. Personalized dosimetry will be calculated for each subject so that subsequent treatments will be estimated to remain within the absorbed cumulative dose limits of 28Gy and 35Gy for kidneys and salivary glands, adjusted iteratively over the 4 remaining treatment cycles separated by 8 weeks. Up to 32 subjects will be enrolled to continue efficacy evaluation.

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Findings from Research

The UpFrontPSMA trial is evaluating the effectiveness and safety of combining lutetium-177 (177 Lu)-PSMA-617 with docetaxel in 140 men with newly diagnosed metastatic hormone-naïve prostate cancer, aiming to determine the proportion of patients achieving undetectable PSA levels after 12 months.

This study is significant as it compares the experimental treatment to standard docetaxel therapy while all patients receive continuous androgen deprivation therapy, potentially providing insights into improved treatment strategies for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). Dhiantravan, N., Emmett, L., Joshua, AM., et al.[2021]

In a phase 2 trial involving 30 men with metastatic castration-resistant prostate cancer, 57% achieved a significant PSA decline of 50% or more after treatment with Lutetium-177 [177Lu]-PSMA-617, indicating its efficacy in this patient population.

The treatment was associated with low toxicity, with the most common side effects being mild dry mouth and transient nausea, and it also led to clinically meaningful improvements in pain and quality of life for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Hofman, MS., Violet, J., Hicks, RJ., et al.[2021]

Lutetium-177 prostate-specific membrane antigen-617 therapy showed promising efficacy in treating metastatic castration-resistant prostate cancer, with 68% of patients experiencing a decrease in serum prostate-specific antigen levels and significant reductions in pain scores after treatment.

While the treatment was effective, it also led to notable adverse effects, including severe leukopenia in one patient and thrombocytopenia in three patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177 Prostate-Specific Membrane Antigen-617 Treatment in Metastatic Castration-Resistant Prostate Adenocarcinoma: Results of Single-Center Experience. Maman, A.[2023]

The ENZA-p trial is investigating the safety and efficacy of combining lutetium-177 (177 Lu)-PSMA-617 with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), aiming to improve prostate-specific antigen (PSA) progression-free survival (PFS) in high-risk patients.

This phase 2 trial will enroll 160 participants and assess various outcomes, including overall survival and quality of life, while also identifying potential biomarkers to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). Emmett, L., Subramaniam, S., Joshua, AM., et al.[2022]

In a study involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), Lutetium-177 PSMA-617 showed a best prostate-specific antigen response rate of 60%, compared to 40% for docetaxel, demonstrating its efficacy as a treatment option.

177Lu-PSMA-617 was associated with fewer severe adverse events and significantly improved quality of life compared to docetaxel, suggesting it may be a safer alternative that could be used earlier in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. Satapathy, S., Mittal, BR., Sood, A., et al.[2022]

In a study of 75 patients with metastatic prostate cancer, 6 were excluded from Lutetium-177 [177Lu]-PSMA-617 treatment due to PSMA-negative/FDG-positive discordance, but 89 suitable targets for biology-guided radiotherapy (BgRT) were identified.

The research suggests that combining BgRT with Lutetium-177 [177Lu]-PSMA-617 is feasible for treating patients with discordant metastases, particularly highlighting that bone and lung metastases are the most suitable candidates for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) has become a promising treatment option for neuroendocrine tumors and prostate cancer, with Lutathera® and Pluvicto® being key approved therapies.

The review emphasizes the need for comprehensive safety data and optimized procedures for using 177Lu radiopharmaceuticals, aiming to improve the risk-benefit balance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. Ladrière, T., Faudemer, J., Levigoureux, E., et al.[2023]

Lutetium-177 PSMA treatment is more likely to be effective in metastatic castration-resistant prostate cancer patients who have high baseline PSMA expression levels, particularly in bone lesions, as indicated by significant differences in SUVmax, PSMA TV, and TL PSMA values after treatment.

The study identified specific cutoff values for predicting treatment response, with a sensitivity of 91.8% for SUVmax greater than 10.50, suggesting that these parameters can help clinicians determine which patients are more likely to benefit from Lu177 PSMA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Ga68 PSMA PET/CT imaging in Lu177 PSMA treatment planning in metastatic castration-resistant prostate cancer. Erdogan, M., Sengul, SS., Cetin, B., et al.[2022]

177Lu-DKFZ-PSMA-617 is a safe and promising treatment for patients with metastatic prostate cancer, with individualized dosimetry calculations showing specific absorbed doses for organs like kidneys and salivary glands.

The study involved 10 patients with a mean age of 71.4 years, highlighting significant inter-individual variations in organ dose, which underscores the importance of personalized treatment planning for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Specific Dosimetry in Radioligand Therapy (RLT) for Metastatic Prostate Cancer Using 177Lu-DKFZ-PSMA-617. Mahmoudi, E., Pirayesh, E., Deevband, MR., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). [2021]

2. England pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. [2021]

3. Turkey pubmed.ncbi.nlm.nih.gov

Lutetium-177 Prostate-Specific Membrane Antigen-617 Treatment in Metastatic Castration-Resistant Prostate Adenocarcinoma: Results of Single-Center Experience. [2023]

4. England pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). [2022]

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

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

The role of Ga68 PSMA PET/CT imaging in Lu177 PSMA treatment planning in metastatic castration-resistant prostate cancer. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Patient-Specific Dosimetry in Radioligand Therapy (RLT) for Metastatic Prostate Cancer Using 177Lu-DKFZ-PSMA-617. [2022]