15 Participants Needed

Vorinostat + 177Lu-PSMA-617 for Metastatic Prostate Cancer

MS
Overseen ByMichael Schweizer
Age: Any Age
Sex: Male
Trial Phase: Phase 2
Sponsor: University of Washington
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining vorinostat and 177Lu-PSMA-617 can effectively target metastatic prostate cancer that resists standard hormone treatments (castration-resistant). Vorinostat stops cancer cell growth, while 177Lu-PSMA-617 (also known as Lutetium Lu 177 vipivotide tetraxetan or Pluvicto) is a radioactive therapy targeting prostate cancer cells. The goal is to determine if this combination can more effectively kill cancer cells in patients whose cancer does not show strong markers (PSMA-low) typically used for targeting. Men with a confirmed diagnosis of prostate cancer that is resistant to standard hormone therapy and has spread beyond the prostate are potential candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a 2-week period without taking androgen receptor-signaling inhibitors and at least 1 week without steroids before starting treatment. If you are on these medications, you will need to stop them for the specified time before participating.

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

Research has shown that vorinostat has been tested in patients with advanced prostate cancer and is generally well-tolerated. Some patients experienced side effects like tiredness, diarrhea, and nausea, but these are usually manageable.

The FDA has approved Lutetium Lu 177 Vipivotide Tetraxetan for treating a specific type of prostate cancer, indicating it has passed safety tests for that purpose. Studies indicate that this treatment is generally well-tolerated, with dry mouth and nausea as the most common side effects. These side effects are often mild and manageable with standard care.

Overall, both treatments have been studied and are considered safe within their respective trials. However, discussing personal health with a healthcare provider before joining any trial is important.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about using Vorinostat + 177Lu-PSMA-617 for metastatic prostate cancer because this combination offers a unique approach to treatment. Unlike traditional therapies like hormone therapy and chemotherapy, 177Lu-PSMA-617 targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor while sparing healthy tissue. Vorinostat, a histone deacetylase inhibitor, may enhance the effectiveness of this targeted radiation by making cancer cells more susceptible to treatment. This innovative strategy not only aims to improve precision in attacking cancer cells but also hopes to reduce side effects often associated with conventional treatments.

What evidence suggests that vorinostat and 177Lu-PSMA-617 might be effective for metastatic prostate cancer?

This trial will evaluate the combination of vorinostat and 177Lu-PSMA-617 for metastatic prostate cancer. Research has shown that vorinostat, a drug that inhibits enzymes necessary for cancer cell growth, holds promise for treating advanced prostate cancer that no longer responds to hormone therapy. In earlier studies, vorinostat slowed the disease in some patients for at least six months. Meanwhile, 177Lu-PSMA-617, a targeted radioactive treatment, has been approved for this type of prostate cancer and has shown positive results. Studies found it extended patients' lives and reduced cancer markers in many cases. This trial will test whether combining these treatments enhances their effectiveness for patients with a specific type of prostate cancer called PSMA-low mCRPC.14678

Who Is on the Research Team?

MS

Michael Schweizer

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that is resistant to hormone therapy and has low levels of a protein called PSMA may join this trial. They should have tried at least one chemotherapy and be in fairly good health, with their major organs functioning well. Men must agree to use two effective birth control methods during the study.

Inclusion Criteria

If you and your partner can have children and are sexually active, you must agree to use two very effective forms of birth control while taking the study drug and for 3 months after stopping the drug to avoid getting pregnant.
Your white blood cell count is high enough.
My prostate cancer has been confirmed through a biopsy.
See 12 more

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 vorinostat orally once a day for 28 days, followed by gallium Ga 68 gozetotide IV and a PET scan. Treatment with 177Lu-PSMA-617 IV may occur on day 1 of each cycle, repeating every 6 weeks for up to 6 cycles.

36 weeks
6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 8 weeks for 6 months and then every 12 weeks for up to 2 years.

2 years
Regular visits every 8-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Lutetium Lu 177 Vipivotide Tetraxetan
  • Vorinostat
Trial Overview The trial is testing if combining Vorinostat (a drug that blocks enzymes needed for cell growth) with a radioactive treatment called 177Lu-PSMA-617 can effectively kill tumor cells in men whose prostate cancer has spread but shows low levels of PSMA.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (vorinostat, 177Lu-PSMA-617)Experimental Treatment10 Interventions

Lutetium Lu 177 Vipivotide Tetraxetan is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Pluvicto for:
🇪🇺
Approved in European Union as Pluvicto for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials
1,858
Recruited
2,023,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials
583
Recruited
1,341,000+

Novartis

Industry Sponsor

Trials
1,646
Recruited
2,778,000+
Vasant Narasimhan profile image

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye profile image

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Institute for Prostate Cancer Research (IPCR)

Collaborator

Trials
1
Recruited
20+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

177Lu-vipivotide tetraxetan is a targeted radiopharmaceutical that effectively treats metastatic castration-resistant prostate cancer (mCRPC) by delivering beta-radiation directly to cancer cells, demonstrating safety and tolerability in clinical trials.
Approved by the FDA in March 2022 based on the VISION trial, this therapy is particularly beneficial for patients who have already undergone androgen receptor pathway inhibition and taxane-based chemotherapy, highlighting its role as a new treatment option in advanced prostate cancer management.
Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer.Shah, H., Ravi, P., Sonpavde, G., et al.[2023]
In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of [177Lu]Lu-PSMA-617 to standard care significantly delayed the time to first symptomatic skeletal event, with a median of 11.5 months compared to 6.8 months for standard care alone.
Patients receiving [177Lu]Lu-PSMA-617 also reported improved health-related quality of life and less pain, although there were some serious adverse events, including hematological issues, indicating the need for careful monitoring during treatment.
Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial.Fizazi, K., Herrmann, K., Krause, BJ., et al.[2023]
Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is the first FDA-approved targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC), specifically for patients with high levels of prostate-specific membrane antigen (PSMA).
This treatment works by binding to PSMA, which is overexpressed in prostate cancer cells, allowing targeted radiation to damage DNA and induce cell death, making it a promising option in precision medicine for individualized cancer therapy.
Lutetium Lu 177 vipivotide tetraxetan for prostate cancer.Liu, X., Fang, GC., Lu, H., et al.[2023]

Citations

Clinical outcomes of lutetium-177-vipivotide tetraxetan in ...In this retrospective study of 177 Lu, we see similar PSA and PSA50 responses to reported trials. However, PFS was shorter, and mortality was higher.
Patient characteristics and overall survival with lutetium ...The median overall survival from the start of ¹⁷⁷Lu-PSMA-617 therapy was 15.3 months (95% CI: 14.6–16.3), with 137 of 643 patients (21.3%) ...
Lu-177 PSMA in Survival of Metastatic Castration-Resistant ...This comparative effectiveness research investigates factors associated with the difference in the observed effect of lutetium Lu 177 ...
PSMAddition data show Novartis Pluvicto™ delays ...PluvictoTM plus standard of care (ARPI + ADT) significantly reduced risk of progression or death by 28% (HR 0.72) versus SoC alone, ...
Lutetium Lu 177 Vipivotide Tetraxetan Efficacy and Toxicity ...68.9% of the cohort observed PSA biomarker improvement of ≥10%, and 55.6% with ≥50% PSA reduction. Three patients (6.7%) achieved a complete ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/36811416/
Lutetium Lu 177 vipivotide tetraxetan for prostate cancerLutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation.
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 on ...
Clinical Trials Using Lutetium Lu 177 Vipivotide TetraxetanReview the clinical trials studying lutetium lu 177 vipivotide tetraxetan on this list and use the filters to refine the results by age and location.
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