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

Overseen By Michael Schweizer

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: HDAC inhibitors, Warfarin

Disqualifiers: Metastatic neuroendocrine, HIV, Hepatitis, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 15

Duration: 36 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well vorinostat works in treating patients with prostate-specific membrane antigen (PSMA)-low castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) (mCRPC). Prostate cancer that has not spread to other parts of the body (localized) is typically treated through surgery or radiotherapy, which for many men is curable. Despite definitive local therapy, cancer that has come back after a period of improvement (recurrent) disease develops in 27-53% of men. Often this is detected by measurement of prostate-specific antigen (PSA) without visible evidence of metastatic disease. Lutetium Lu 177 vipivotide tetraxetan (177Lu-prostate specific membrane antigen \[PSMA\]-617) is a new small molecule PSMA-targeted radioactive therapy that has been approved by the Food and Drug Administration for the treatment of adult patients with PSMA-positive mCRPC who have been treated with androgen receptor inhibitors and taxane-based chemotherapy. Vorinostat is used to treat various types of cancer that does not get better, gets worse, or comes back during or after treatment with other drugs. Vorinostat is a drug which inhibits the enzyme histone deacetylase and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat and 177Lu-PSMA-617 may kill more tumor cells in in patients with PSMA-low mCRPC.

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.

What data supports the effectiveness of the drug Lutetium Lu 177 vipivotide tetraxetan for metastatic prostate cancer?

The drug Lutetium Lu 177 vipivotide tetraxetan has been shown to improve survival in patients with metastatic prostate cancer, as demonstrated in the VISION trial. Patients receiving this drug lived longer on average compared to those who received standard care alone. ^{1 2 3 4 5}

Is the combination of Vorinostat and 177Lu-PSMA-617 safe for humans?

The safety of 177Lu-PSMA-617 (also known as Pluvicto) has been evaluated in clinical trials for prostate cancer, showing it is generally safe when used as directed, with some patients experiencing side effects. However, specific safety data for the combination with Vorinostat is not available in the provided research. ^{1 2 3 4 5}

What makes the drug Vorinostat + 177Lu-PSMA-617 unique for treating metastatic prostate cancer?

This drug combines Vorinostat, which modifies gene expression, with 177Lu-PSMA-617, a radioligand that specifically targets and delivers radiation to prostate cancer cells, offering a novel approach by directly attacking cancer cells while potentially improving survival and quality of life compared to standard treatments. ^{1 2 3 4 6}

Research Team

Michael Schweizer

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

Your white blood cell count is high enough.

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.

My prostate cancer has been confirmed through a biopsy.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Treatment (vorinostat, 177Lu-PSMA-617) Experimental Treatment 10 Interventions

Patients receive vorinostat PO QD for 28 days and then receive gallium Ga 68 gozetotide IV and undergo a PET scan on trial. Patients may go on to receive 177Lu-PSMA-617 IV per SOC on day 1 of each cycle. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT and bone scan on trial and during follow-up, as well as a FDG PET/CT during screening and on trial and SPECT/CT on trial. Patients undergo blood sample collection on trial and may also optionally undergo biopsy during screening and on trial.

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

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer (mCRPC) in adults who have been treated with androgen receptor inhibitors and taxane-based chemotherapy

Approved in European Union as Pluvicto for:

• Treatment of adult patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitors and taxane-based chemotherapy

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

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

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+

Findings from Research

Lutetium Lu 177 vipivotide tetraxetan (PLUVICTO™) is a targeted radioligand therapy approved in the USA for treating metastatic castration-resistant prostate cancer (mCRPC) that expresses prostate-specific membrane antigen (PSMA), based on positive results from the phase 3 VISION trial.

This therapy specifically targets PSMA, which is overexpressed in prostate cancer cells, allowing for a more effective treatment option for patients who have already undergone other therapies like androgen receptor inhibition and taxane-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Keam, SJ.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. Shah, H., Ravi, P., Sonpavde, G., et al.[2023]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Liu, X., Fang, GC., Lu, H., et al.[2023]

The VISION trial demonstrated that lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) significantly improves progression-free and overall survival in patients with metastatic castration-resistant prostate cancer compared to standard of care (SoC).

In terms of cost-effectiveness, 177Lu-PSMA-617 therapy resulted in an incremental cost-effectiveness ratio of $200,708 per quality-adjusted life year (QALY), indicating that while it is more expensive than SoC, it may still be considered cost-effective under certain willingness-to-pay thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer. Mehrens, D., Kramer, KKM., Unterrainer, LM., et al.[2023]

References

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

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. [2023]

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

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. [2023]

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

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer. [2023]