177Lu-J591 + Ketoconazole for Prostate Cancer

Not currently recruiting at 9 trial locations

Overseen By GUONC Research Team

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Ketoconazole, Hydrocortisone

Must not be taking: Adrenal inhibitors, Finasteride

Disqualifiers: Active infection, Heart disease, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for effectiveness against prostate cancer. The trial uses an experimental drug, 177Lu-J591 (a radiolabeled antibody therapy), along with ketoconazole (an antifungal medication) and hydrocortisone (a corticosteroid). Participants will be compared to those receiving a placebo version, 111In-J591. Ideal participants have prostate cancer confirmed through tests, a rise in PSA (a protein related to prostate cancer), and a high risk of cancer spreading, but no signs of it spreading or recurring locally. The study aims to determine if this combination can effectively tackle prostate cancer when other treatments no longer work. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in prostate cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does mention that certain medications like adrenal hormone inhibitors, finasteride, and dutasteride should be stopped at least 4 weeks before enrollment. If you are on corticosteroids, you must either stop them or show progression on a stable dose.

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

Studies have shown that 177Lu-J591 is generally well-tolerated. In some cases, it caused temporary low blood cell counts, known as myelosuppression, but these effects did not last. The treatment effectively targeted tumors, offering promise for prostate cancer patients.

Research indicates that ketoconazole is also safe for treating prostate cancer. It may cause side effects such as stomach issues and tiredness. Changes in liver function and skin reactions have also been reported, but these can be managed with proper monitoring.

In summary, both 177Lu-J591 and ketoconazole have been tested and are generally safe, with some side effects that require monitoring. ^{1 2 3 4 5}

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

Researchers are excited about the combination of 177Lu-J591 and ketoconazole for prostate cancer due to its unique approach to targeting cancer cells. Unlike standard treatments like hormone therapy or chemotherapy, 177Lu-J591 is a radiolabeled monoclonal antibody that specifically seeks out prostate cancer cells, delivering targeted radiation directly to them. This precision aims to minimize damage to healthy cells and potentially reduce side effects. Additionally, combining this with ketoconazole, which helps block testosterone production, could enhance the overall effectiveness in combating the cancer.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that 177Lu-J591, one of the treatments studied in this trial, yields promising results for prostate cancer. In earlier studies, many patients experienced a noticeable drop in their prostate-specific antigen (PSA) levels, a key indicator for monitoring prostate cancer. Specifically, 87.5% of patients saw some decrease in PSA levels, and 58.8% experienced a reduction of more than 30%. This treatment has also been linked to longer survival in patients with advanced prostate cancer that no longer responds to standard hormone therapy. In this trial, 177Lu-J591 will be tested in combination with ketoconazole. These findings suggest that 177Lu-J591 could effectively manage prostate cancer when used with ketoconazole. ^{1 2 3 6 7}

Who Is on the Research Team?

Scott T Tagawa, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's worsened after surgery or radiotherapy can join. They must have a rising PSA level, no signs of the cancer spreading significantly, and low testosterone. Participants should not be at high risk of other serious illnesses and agree to use contraception if they can father children.

Inclusion Criteria

My prostate cancer was confirmed by a lab test and I've had surgery or radiotherapy.

My prostate cancer is worsening despite hormone therapy.

Exclusion Criteria

My platelet count is below 150,000 or I have a known platelet disorder.

Serum creatinine >2.5 mg/dL

AST (SGOT) >2x ULN

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Ketoconazole and hydrocortisone for 4 weeks followed by 177Lu-J591 or 111In-J591 infusion, continuing ketoconazole and hydrocortisone

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including scans and PSA level assessments

18 months

Regular visits every 4 weeks

Long-term follow-up

Participants continue to be monitored for PSA progression or end of study

Up to 100 months

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-J591
• Hydrocortisone
• Ketoconazole

Trial Overview The trial is testing an experimental drug called 177Lu-J591 combined with ketoconazole and hydrocortisone on prostate cancer patients. It aims to see how effective this combination is in controlling the progression of the disease.

How Is the Trial Designed?

Group I: 1. 177Lu-J591 + Ketoconazole Experimental Treatment 3 Interventions

Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 177Lu-J591 Infusion, continue ketoconazole and hydrocortisone

Group II: 2. 111In-J591 + Ketoconazole Placebo Group 3 Interventions

Ketoconazole 400 mg 3 times a day plus hydrocortisone 20 mg AM, 10 mg PM x 4 weeks followed by 111In-J591 (placebo) Infusion, continue ketoconazole and hydrocortisone

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a study of 125 men with metastatic castrate-resistant prostate cancer treated with 177LuPSMA, personalizing treatment intervals based on early response biomarkers (PSA and SPECT imaging) led to improved progression-free survival (PFS) and overall survival (OS), with a median OS of 16.8 months overall.

The study found that 35% of patients could take treatment breaks after showing a marked response, resulting in a median PFS of 12.1 months for this group, compared to shorter PFS for those with less favorable responses, highlighting the potential for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT). Emmett, L., John, N., Pathmanandavel, S., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31012963/

Phase 1/2 study of fractionated dose lutetium-177-labeled anti ... Fractionated administration of 177 Lu-J591 allowed higher cumulative radiation dosing. The frequency and depth of PSA decrease, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7100619/

Review of Lutetium-177-labeled Anti-prostate-specific ... Radioimmunotherapy with a monoclonal antibody (mAb), J591, has shown promising results in the treatment of prostate cancer.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.82

Survival outcomes of patients (pts) with metastatic ... Survival outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177-PSMA-617 (Lu) based ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.32072

Phase 1/2 study of fractionated dose lutetium‐177–labeled ... This dose showed a greater decrease in prostate-specific antigen (PSA) levels and longer survival (87.5% with any PSA decrease, 58.8% with >30% ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00859781

NCT00859781 | 177Lu Radiolabeled Monoclonal Antibody ... The purpose of this study is to test the effectiveness of the experimental drug, 177Lu-J591 in combination with ketoconazole and hydrocortisone against prostate ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3778101/

Phase II study of lutetium-177 labeled anti-prostate-specific ... A single dose of 177 Lu-J591 was well-tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose- ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143920302593

Phase I trial of docetaxel plus lutetium-177-labeled anti– ... Initial studies of trace-labeled J591 demonstrated safety and tumor targeting, leading to clinical trials of 177Lu-J591. Initial phase I and II trials of 177Lu- ...