177Lu-J591 + Ketoconazole for Prostate Cancer

Recruiting at 8 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

55 Participants Needed

Trial Summary

What is the purpose of this trial?

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

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.

What data supports the effectiveness of the drug 177Lu-J591 + Ketoconazole for prostate cancer?

Research shows that ketoconazole, when used with hydrocortisone, can help reduce PSA levels (a marker of prostate cancer activity) in patients with hormone-refractory prostate cancer, with some patients experiencing significant decreases in PSA levels. Additionally, 177LuPSMA, a similar treatment to 177Lu-J591, has been effective in treating metastatic castrate-resistant prostate cancer, suggesting potential benefits for 177Lu-J591 in similar conditions. ^{1 2 3 4 5}

Is the combination of 177Lu-J591 and Ketoconazole safe for treating prostate cancer?

Ketoconazole, used in treating advanced prostate cancer, generally has a reasonable safety profile. Common side effects include stomach issues, tiredness, liver changes, and skin reactions, but serious effects can often be managed with simple measures. ^{1 6 7 8 9}

How does the drug 177Lu-J591 + Ketoconazole differ from other prostate cancer treatments?

The combination of 177Lu-J591, a targeted radiolabeled antibody, with Ketoconazole, which lowers testosterone levels, offers a unique approach by combining targeted radiation with hormone suppression, potentially enhancing effectiveness against prostate cancer compared to traditional hormone therapies alone. ^{1 7 10 11 12}

Research Team

Scott T Tagawa, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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.

High risk of systemic progression defined as: Rising PSA with Absolute PSA > 20 ng/mL and/or PSA doubling time < 8 months, No evidence of local recurrence or distant metastases, Age >18 years, Serum testosterone < 50 ng/ml, Patients capable of fathering children must agree to use an effective method of contraception for the duration of the trial, Subjects on bisphosphonate therapy must be on a stable dose and must have started therapy > 4 weeks prior to protocol therapy, Ability to understand and the willingness to sign a written informed consent document

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

R75251 in prostate cancer patients in progression after first-line hormonal treatment. [2022]

2. Serbia pubmed.ncbi.nlm.nih.gov

An evaluation of high-doses ketoconazole with hydrocortisone substitution in hormone-refractory prostate cancer. [2019]

3. England 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). [2023]

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

Phase II study of ketoconazole plus granulocyte-macrophage colony-stimulating factor for prostate cancer: effect of extent of disease on outcome. [2013]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy of low dose ketoconazole therapy for Chinese patients with castration resistant prostate cancer]. [2013]

6. New Zealand pubmed.ncbi.nlm.nih.gov

The treatment of advanced prostate cancer with ketoconazole: safety issues. [2022]

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

Ketoconazole: a novel and rapid treatment for advanced prostatic cancer. [2019]

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

Significant prostate-specific antigen (PSA) response to low-dose ketoconazole in a patient with non-metastatic androgen-independent prostate cancer (AIPC) and a review of the literature. [2013]

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

Ketoconazole therapy in advanced prostatic cancer. [2019]

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

Efficacy of microtubule-active drugs followed by ketoconazole in human metastatic prostate cancer cell lines. [2015]

11. Canada pubmed.ncbi.nlm.nih.gov

Effects of high-dose ketoconazole on patients who have androgen-independent prostatic cancer. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Ketoconazole high dose in the hormonal treatment of advanced carcinoma of the prostate. A pilot study. [2019]