Tuvusertib for Refractory Prostate Cancer

Recruiting in Palo Alto (17 mi)

+27 other locations

Overseen by Jacob Orme

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must be taking: Androgen deprivation therapy

Must not be taking: Proton pump inhibitors

Disqualifiers: Uncontrolled illness, QT interval > 470, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests M1774, a drug taken by mouth, in patients with hard-to-treat prostate cancer with a specific genetic mutation. The drug aims to stop cancer cells from growing by blocking enzymes they need. It could help shrink or stabilize these difficult-to-treat tumors.

Will I have to stop taking my current medications?

The trial requires you to stop taking proton pump inhibitors (medications that reduce stomach acid) and certain other drugs that affect liver enzymes (CYP3A4 or CYP1A2) and transport proteins (hMATE1 or hMATE2-K).

What data supports the effectiveness of the drug Tuvusertib for refractory prostate cancer?

The research highlights the need for new treatments for metastatic castration-resistant prostate cancer and mentions various targeted therapies being tested, including those affecting similar pathways as Tuvusertib. While specific data on Tuvusertib is not provided, the exploration of targeted therapies in prostate cancer suggests a potential for effectiveness. ^{1 2 3 4 5}

What makes the drug Tuvusertib unique for treating refractory prostate cancer?

Tuvusertib is a novel treatment option for refractory prostate cancer, which is a condition where the cancer does not respond to standard therapies like docetaxel. Unlike other treatments, Tuvusertib may target specific molecular pathways involved in cancer growth, offering a new approach for patients with limited options. ^{1 4 6 7 8}

Eligibility Criteria

This trial is for adults with hard-to-treat prostate cancer that has a specific SPOP gene mutation. Participants must have measurable disease, be on hormone therapy or surgically castrated, and have adequate organ function. People with controlled HIV or hepatitis are eligible; those with certain heart conditions may join after assessment. Women of childbearing potential and men must agree to use contraception.

Inclusion Criteria

I have chronic hepatitis B but it's under control with treatment.

Ability to understand and willingness to sign a written informed consent document

Creatinine clearance >= 60 mL/min

Exclusion Criteria

I have recovered from side effects of previous cancer treatments, except for hair loss.

Patients receiving any other investigational agents

Patients with uncontrolled intercurrent illness

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tuvusertib orally every day on days 1-14 of each 21-day cycle. Biopsy, imaging, and blood sample collection are conducted throughout the trial.

Up to 2 years

Follow-up

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

2 years

Treatment Details

Interventions

• M1774 (Enzyme Inhibitor)

Trial Overview The trial tests M1774's effectiveness in shrinking or stabilizing refractory SPOP-mutant prostate cancer by inhibiting enzymes needed for tumor cell growth. It involves various assessments like biospecimen collection, imaging (ultrasound, CT, MRI, PET), and biopsy to monitor the treatment's impact.

Participant Groups

Group I: Treatment (tuvusertib) Experimental Treatment 7 Interventions

Patients receive tuvusertib PO QD on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, MRI, CT, PET/MRI, PET/CT or U/S and collection of blood samples throughout the trial.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UT Southwestern Clinical Center at Richardson/Plano Richardson, TX

University of Wisconsin Carbone Cancer Center - University Hospital Madison, WI

Siteman Cancer Center-South County Saint Louis, MO

UT Southwestern/Simmons Cancer Center-Dallas Dallas, TX

More Trial Locations

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Novel targeted therapeutics for metastatic castration-resistant prostate cancer. [2021] Virtually all patients that succumb to prostate cancer die of metastatic castration-resistant disease. Although docetaxel is the standard of care for these patients and is associated with a modest prolongation of survival, there is an urgent need for novel treatment strategies for metastatic prostate cancer. In the last several years, great strides have been made in our understanding of the biological and molecular mechanisms driving prostate cancer growth and progression, and this has resulted in widespread clinical testing of numerous new targeted therapies. This review discusses some of the key therapeutic agents that have emerged for the treatment of metastatic castration-resistant prostate cancer in the last 5years, with an emphasis on both molecular targets and clinical trial design. These agents include mammalian target of rapamycin (mTOR) pathway inhibitors, anti-angiogenic drugs, epidermal growth factor receptor (EGFR) inhibitors, insulin-like growth factor (IGF) pathway inhibitors, apoptosis-inducing drugs, endothelin receptor antagonists, receptor activator of nuclear factor kappaB (RANK) ligand inhibitors, vitamin D analogues, cytochrome P17 enzyme inhibitors, androgen receptor modulators, epigenetic therapies, vaccine therapies, and cytotoxic T lymphocyte-associated antigen (CTLA)-4 blocking agents.

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

Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer. [2022] Phosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway activation is common in metastatic castration resistant prostate cancer (mCRPC). Buparlisib is an oral, pan-class I PI3 kinase inhibitor.

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

A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naïve castration-resistant prostate cancer. [2022] To investigate the efficacy and safety of combining vandetanib, an orally available multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR), with bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC).

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

Effects of EGFR tyrosine kinase inhibitor erlotinib in prostate cancer cells in vitro. [2018] Erlotinib is a small-molecule tyrosine kinase inhibitor targeted EGFR, known to be overexpressed in a variety of cancers, including prostate cancer. Clinical trials showed insignificant clinical benefit in patients with castration resistant prostate cancer both when EGFR inhibitors were administered as monotherapy or in association with antiandrogens or chemotherapeutics. Why, differently to other tumors, have EGFR inhibitors been so ineffective in human prostate cancer? This is the question that we have set in this report.

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

A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer. [2021] The objective of this trial was to evaluate the clinical effects of sorafenib, a multi-targeted kinase inhibitor, in combination with androgen receptor blockade in patients with castration-resistant prostate cancer.

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05). [2022] Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC).

7. England pubmed.ncbi.nlm.nih.gov

Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer. [2020] Erlotinib is an orally active small-molecule tyrosine kinase inhibitor targeted against human epidermal growth factor receptor 1/epidermal growth factor receptor (ErbB1), known to be overexpressed in a variety of cancers, including prostate cancer.

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

An open-label, single-arm phase two trial of gefitinib in patients with advanced or metastatic castration-resistant prostate cancer. [2018] To determine whether the oral epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa has clinical efficacy in patients with castration-resistant prostate cancer (CRPC).