Lutetium PSMA + SBRT for Prostate Cancer

(LUNAR Trial)

Overseen By Christie Palodichuk

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Androgen deprivation therapy

Disqualifiers: Neuroendocrine carcinoma, Castrate-resistant, 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

93 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if using a radioactive drug, 177-Lutetium-PSMA, before precise radiation therapy can better control prostate cancer that has returned in patients with 1-5 tumors. The drug targets cancer cells directly, and the radiation therapy aims to kill these cells with high precision and fewer side effects. Lutetium-177 (Lu-177) labeled PSMA has shown promising outcomes in treating advanced prostate cancer, including reduced disease progression and improved overall survival.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy or any systemic therapy for another cancer, you may not be eligible to participate.

What data supports the effectiveness of the treatment Lutetium Lu-177 PNT2002 combined with Stereotactic Body Radiation Therapy for prostate cancer?

Research shows that Lutetium-177 PSMA therapy is effective and safe for treating metastatic castration-resistant prostate cancer, improving survival and quality of life. Combining it with targeted radiation therapy like SBRT may enhance its effectiveness by precisely targeting cancer cells. ^{1 2 3 4 5}

Is Lutetium PSMA therapy safe for humans?

Lutetium-177 PSMA therapy has been shown to be a safe treatment option for patients with advanced prostate cancer, with clinical studies indicating it is generally well-tolerated. ^{1 2 5 6 7}

What makes the Lutetium Lu-177 PNT2002 treatment unique for prostate cancer?

Lutetium Lu-177 PNT2002 is unique because it combines a radiolabeled molecule that specifically targets prostate-specific membrane antigen (PSMA) on cancer cells with stereotactic body radiotherapy (SBRT), offering a personalized and targeted approach for treating metastatic prostate cancer. This combination aims to enhance the effectiveness of treatment by precisely targeting cancer cells while minimizing damage to surrounding healthy tissue. ^{1 2 5 6 8}

Research Team

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

Men over 18 with prostate adenocarcinoma that's come back in 1-5 spots after treatment can join. They need good blood counts, liver and kidney function, and must be feeling well enough to do daily activities. No recent hormone therapy for cancer or other solid tumors being treated, no lying flat issues, or allergies to the radioactive drug used.

Inclusion Criteria

Hemoglobin >= 9 g/dL

White blood cell count >= 2.5 × 10^9/L

Partner and patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal investigator during the study and for 3 months after last study drug administration

Exclusion Criteria

My prostate cancer is of the neuroendocrine or small cell type.

I have received hormone therapy for cancer within the last 6 months.

My kidney function is below normal levels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 177Lu-PNT2002 intravenously on days -112 and -56

8 weeks

2 visits (in-person)

Stereotactic Body Radiotherapy (SBRT)

Participants undergo SBRT to all lesions for 1, 3, or 5 treatment doses over 10-20 days

2-3 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Visits at 1, 3, 6, 9, and 12 months, then every 6 months

Treatment Details

Interventions

• Lutetium Lu-177 PNT2002
• Stereotactic Body Radiation Therapy

Trial Overview The LUNAR study is testing if a radioactive drug called 177-Lutetium-PSMA given before precise radiation therapy (SBRT) helps control recurrent prostate cancer better. The idea is that the drug targets tumor cells without hurting normal ones and makes SBRT more effective.

Participant Groups

Group I: Arm 2 (177Lu-PNT2002, SBRT) Experimental Treatment 3 Interventions

Patients receive 177Lu-PNT2002 IV over 1-10 minutes on days -112 and -56 in the absence of disease progression or unacceptable toxicity. Beginning on day 1, patients then undergo SBRT to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm 1 (SBRT) Active Control 2 Interventions

Beginning on day 1, patients undergo SBRT to all lesions for 1, 3, or 5 treatment doses (fractions) over the span of 10-20 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company

Industry Sponsor

Trials

5

Recruited

670+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

POINT Biopharma

Industry Sponsor

Trials

6

Recruited

720+

Findings from Research

The LUNAR trial is investigating the efficacy of 177 Lu-PNT2002, a radiolabelled small molecule targeting prostate-specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) for men with oligorecurrent metastatic hormone-sensitive prostate cancer, with 100 patients expected to be enrolled.

This Phase 2 trial aims to determine if adding 177 Lu-PNT2002 to SBRT can improve progression-free survival and other outcomes compared to SBRT alone, potentially offering a new treatment strategy for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LUNAR: a randomized Phase 2 study of 177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol). Ma, TM., Czernin, J., Felix, C., 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]

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 of 84 Asian patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177 PSMA radioligand therapy, the median overall survival was 12.2 months and the median PSA progression-free survival was 5.2 months, indicating promising efficacy.

A significant 51.8% of patients experienced a PSA decline of 50% or more, which was linked to longer overall survival and PSA progression-free survival, while the treatment showed a manageable safety profile with grade 3 hematotoxicity occurring in 13 out of 78 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). Chua, WM., Lam, WW., Tong, AK., et al.[2023]

In a study of 54 patients with advanced metastatic castration-resistant prostate cancer (mCRPC), 79% showed a significant decrease in PSA levels after three cycles of [177Lu]Lu-PSMA-617 radio-ligand therapy, indicating a strong therapeutic response.

The treatment was well-tolerated, with a median overall survival of 119 weeks and a median progression-free survival of 25 weeks, suggesting that PSMA-RLT can be an effective option for patients with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks. Rasul, S., Hacker, M., Kretschmer-Chott, E., et al.[2021]

Treatment with lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA) significantly reduces prostate-specific antigen (PSA) levels in patients with advanced metastatic prostate cancer, especially after the first treatment cycle.

The therapy shows a beneficial effect on reducing lymph node metastasis, while also indicating potential negative impacts on visceral metastasis, highlighting its efficacy in managing certain aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. Rathore, R., Rangrej, SB., Kieme, I., et al.[2023]

References

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

LUNAR: a randomized Phase 2 study of 177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol). [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

Factors affecting overall survival and progression-free survival in patients with metastatic castration resistant prostate cancer received 177Lu PSMA I&T therapy. [2021]

3. 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]

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. Australia pubmed.ncbi.nlm.nih.gov

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study). [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Prostate-specific membrane antigen theranostics: therapy with lutetium-177. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. [2023]