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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for men with prostate cancer that has spread and resists standard hormone treatments. The treatment uses a special type of radiation therapy called 177Lu-HTK03170, designed to target and kill cancer cells more precisely. The trial aims to find the safest dose and evaluate the treatment's effectiveness in reducing cancer. Men whose prostate cancer has worsened despite advanced hormone therapies and who show specific signs of cancer progression might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that the treatment 177Lu-HTK03170 is well-tolerated by people with prostate cancer. Studies have examined how the treatment moves through the body and its effects on organs. Researchers administered different doses to determine safe amounts. These studies reported no serious safety issues, which is encouraging.

This treatment is currently in phase 1 and 2 trials, meaning it is still being tested for safety and effectiveness. Treatments at this stage have usually undergone enough testing to suggest safety for further study, but more information is needed for confirmation.

Overall, current findings are promising for safety, but additional research will help confirm these results. ^{1 2 3 4 5}

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

Researchers are excited about 177Lu-HTK03170 for prostate cancer because it offers a unique approach compared to current treatments like surgery, radiation, and hormone therapy. This treatment uses a radioactive compound, 177Lu, which specifically targets cancer cells, delivering radiation directly to the tumor while sparing healthy tissue. This targeted mechanism could potentially lead to more effective outcomes with fewer side effects. Additionally, personalized dosimetry allows for tailored treatment plans, optimizing safety and effectiveness for each patient.

What evidence suggests that 177Lu-HTK03170 might be an effective treatment for prostate cancer?

Research shows that 177Lu-HTK03170, the investigational treatment in this trial, delivers radiation directly to prostate cancer cells. This method aims to attack cancer cells while sparing healthy tissue. Previous studies have found that similar treatments helped patients with prostate cancer unresponsive to standard hormone therapy. Early results suggest this therapy could benefit patients with a specific type of advanced prostate cancer. The treatment uses a compound that targets and attaches to prostate cancer cells, directing the radiation precisely where needed. This targeted approach shows promise in shrinking tumors and slowing cancer growth. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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

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

Life expectancy of > 6 months

Willing and able to provide consent

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase I

Subjects receive up to 5 cycles of 177Lu-HTK03170 with dosimetry and IA escalation based on safety and efficacy

40 weeks

Multiple visits for each cycle, including dosimetry scans on days 1, 3, and 10

Treatment Phase II

Subjects receive treatment at the MTD or 1625 MBq, with personalized dosimetry over 4 cycles

32 weeks

Multiple visits for each cycle, including dosimetry scans on days 1, 3, and 10

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 4 months

24 months

Regular visits every 4 months

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/252015

First in human evaluation of 177Lu-HTK03170: Biodistribution ... This study aims to investigate the biodistribution and dosimetry of 177 Lu-HTK03170 in metastatic castration-resistant prostate cancer (mCRPC) patients.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40306965/

A Phase I/II Study of [177Lu]Lu-HTK03170 with ... This phase I/II clinical trial aims to evaluate the safety, dosimetry, and efficacy of [ 177 Lu]Lu-HTK03170 in patients with PSMA-positive mCRPC.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05570994

177Lu-HTK03170 in mCRPC With PSMA Positive Disease This study will determine the safe initial injected activity of the radioligand therapy 177Lu-HTK03170 for the measurement of dosimetry and initiation of ...

4. withpower.com withpower.com/trial/177lu-htk03170-for-prostate-cancer-907ff

177Lu-HTK03170 for Prostate Cancer · Info for Participants Lutetium-177 prostate-specific membrane antigen-617 therapy showed promising efficacy in treating metastatic castration-resistant prostate cancer, with 68 ...

5. openmedscience.com openmedscience.com/advancing-prostate-cancer-treatment-the-role-of-lutetium-177-htk03170-and-gallium-68-htk03149-in-psma-targeted-therapy/

Lutetium-177 HTK03170 for Prostate Cancer Lutetium-177 HTK03170 delivers targeted beta radiation therapy to PSMA-positive prostate cancer cells, improving treatment outcomes.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10071785/

Safety and Survival Outcomes of 177Lu-Prostate-Specific ... 177 Lu-PSMA treatment was well tolerated in patients who had received prior 223 Ra. 223 Ra use before 177 Lu-PSMA is feasible and can be considered for future ...