Tuvusertib for Refractory Prostate Cancer

Recruiting at 27 trial locations

Overseen By Janaki N. Sharma

Age: 18+

Sex: Male

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

20 Participants Needed

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}

Research Team

Jacob Orme

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

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

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

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Docetaxel remains the standard treatment for metastatic castration-resistant prostate cancer, but there is a critical need for new therapies due to its limited survival benefits.

Recent advancements have led to the development of various targeted therapies, including mTOR inhibitors and EGFR inhibitors, which are currently being tested in clinical trials to improve treatment outcomes for this aggressive form of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel targeted therapeutics for metastatic castration-resistant prostate cancer. Antonarakis, ES., Carducci, MA., Eisenberger, MA.[2021]

In a phase II trial involving 30 men with metastatic castration-resistant prostate cancer (mCRPC), buparlisib showed a low 6-month progression-free survival rate of only 10%, indicating limited efficacy in this patient population.

Concurrent use of enzalutamide significantly reduced buparlisib concentrations and was associated with severe adverse events in some patients, highlighting the need for careful consideration of treatment combinations and dosing strategies.

NCBI (Pubmed)

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. Armstrong, AJ., Halabi, S., Healy, P., et al.[2022]

The combination of vandetanib and bicalutamide in patients with metastatic castration-resistant prostate cancer did not show superior efficacy compared to bicalutamide alone, with similar PSA response rates of 18% for the combination and 19% for bicalutamide alone.

Patients receiving the combination therapy experienced significantly higher rates of treatment discontinuation due to adverse events (42% vs. 5%), indicating that the combination is associated with considerable toxicity and is not recommended for further evaluation.

NCBI (Pubmed)

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. Azad, AA., Beardsley, EK., Hotte, SJ., et al.[2022]

Erlotinib, an EGFR inhibitor, showed reduced effectiveness in treating castration-resistant prostate cancer, particularly when the EGFR/Her2 ratio was low, which was influenced by chronic treatment with bicalutamide.

The study suggests that erlotinib may be more effective in hormone-naive prostate cancer patients rather than those who have undergone hormonal treatment, as low levels of Her2 and a higher EGFR/Her2 ratio were associated with better drug efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of EGFR tyrosine kinase inhibitor erlotinib in prostate cancer cells in vitro. Festuccia, C., Gravina, GL., Biordi, L., et al.[2018]

In a phase 2 trial involving 39 patients with castration-resistant prostate cancer, the combination of sorafenib and bicalutamide resulted in a 47% rate of PSA response or stable disease for at least 6 months, indicating potential efficacy of this treatment approach.

The treatment was associated with some significant side effects, including fatigue and skin rash, but showed promise even in patients who had previously progressed on bicalutamide, suggesting that further research into combining these therapies is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer. Beardsley, EK., Hotte, SJ., North, S., et al.[2021]

Dovitinib demonstrated modest antitumor activity in men with metastatic castration-resistant prostate cancer (mCRPC), with a median progression-free survival (PFS) of 3.67 months and an overall survival (OS) of 13.70 months in a study involving 44 participants.

Patients who had not previously undergone chemotherapy experienced significantly longer PFS (17.90 months) compared to those who had been treated with docetaxel (2.07 months), indicating that dovitinib may be more effective in earlier treatment stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05). Choi, YJ., Kim, HS., Park, SH., et al.[2022]

In a phase II study involving 30 patients with advanced prostate cancer, erlotinib showed moderate toxicity but resulted in clinical benefit for 40% of participants, indicating some effectiveness in improving patient outcomes.

While no patients experienced a decrease in prostate-specific antigen (PSA) levels, 14% had stabilization of PSA, and 10 patients showed a significant increase in PSA-doubling time, suggesting potential for further investigation in earlier stages of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer. Gravis, G., Bladou, F., Salem, N., et al.[2020]

In a phase 2 study involving 51 men with castration-resistant prostate cancer (CRPC), gefitinib showed minimal clinical efficacy, with only 2% of patients achieving a significant reduction in prostate-specific antigen (PSA) levels.

The treatment was associated with notable side effects, leading to dose reductions in 13 patients and withdrawal in 9 due to adverse events, indicating that while some patients maintained stable performance status, the overall response to gefitinib was limited.

NCBI (Pubmed)

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. Pezaro, C., Rosenthal, MA., Gurney, H., et al.[2018]

References

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

Novel targeted therapeutics for metastatic castration-resistant prostate cancer. [2021]

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]

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]

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

Effects of EGFR tyrosine kinase inhibitor erlotinib in prostate cancer cells in vitro. [2018]

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]

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

Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05). [2022]

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

Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer. [2020]

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]