RNR Inhibitor COH29 for Solid Tumors

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Herbal medications

Disqualifiers: Active infection, Heart disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 28 days per course

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called COH29, an RNR inhibitor, which may stop the growth of solid tumors unresponsive to standard treatments. The main goal is to determine the safest and most effective dose of COH29. This treatment could suit individuals with advanced tumors that have spread, cannot be removed, or recur, and who have not found success with other treatments. Participants should be able to swallow pills and have no active heart disease. As a Phase 1 trial, this research focuses on understanding how COH29 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take any other investigational drugs or over-the-counter herbal medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that COH29 has potential based on early tests. Studies in cancer cells and mice demonstrated that it reduced tumor growth with minimal impact on normal cells, suggesting it might be safe for humans. However, this trial is in an early stage, and the treatment is still undergoing safety testing in people. Human data remains limited. So far, COH29 appears well-tolerated, but researchers are still identifying all possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

COH29 is unique because it targets solid tumors by inhibiting ribonucleotide reductase (RNR), an enzyme crucial for DNA synthesis and cell division. Unlike standard chemotherapy options, which broadly attack rapidly dividing cells, COH29 offers a more targeted approach, potentially reducing side effects and improving effectiveness. Researchers are excited about COH29 because its novel mechanism could provide a new avenue for treating tumors that are resistant to existing therapies.

What evidence suggests that COH29 might be an effective treatment for solid tumors?

Research shows that COH29, the investigational treatment in this trial, may help treat solid tumors. Lab studies have found that COH29 slows tumor growth by stopping cancer cells from growing, while leaving normal cells unharmed, suggesting it might be safe to use. COH29 blocks an enzyme that cancer cells need to multiply. Earlier tests demonstrated that COH29 can also prevent cancer cells from spreading to other parts of the body. Overall, these findings suggest that COH29 could be a promising new treatment for patients with difficult-to-treat solid tumors. ^{4 5 6 7 8}

Who Is on the Research Team?

Vincent Chung

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with solid tumors that haven't responded to standard treatments or have no standard options left. They must be able to consent, have a life expectancy over 3 months, and an ECOG status of <=2. Participants need adequate blood counts, organ function, and agree to use contraception. Those with recent heart issues, active breastfeeding, uncontrolled illnesses or taking other investigational drugs can't join.

Inclusion Criteria

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN; AST/ALT =< 5 x ULN if liver metastasis is present

I can take care of myself but might not be able to do heavy physical work.

Absolute neutrophil count >= 1,500 cells/µL

Exclusion Criteria

Patients with uncontrolled undercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements

I am not taking any experimental drugs or herbal medications.

I do not have active heart problems like recent heart attack or uncontrolled heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive RNR inhibitor COH29 orally twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per course

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• COH29

Trial Overview The study tests the safety and optimal dosage of COH29 in patients with advanced solid tumors. COH29 aims to block ribonucleotide reductase which may stop tumor growth. The trial includes lab biomarker analysis and pharmacological studies to understand how the drug works in the body.

How Is the Trial Designed?

Group I: Treatment (RNR inhibitor COH29) Experimental Treatment 3 Interventions

Patients receive RNR inhibitor COH29 PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. withpower.com withpower.com/trial/phase-1-neoplasms-5-2016-a32c2

RNR Inhibitor COH29 for Solid Tumors · Info for Participants COH29 has been tested in cancer cells and mouse models, showing it can reduce tumor growth with little effect on normal cells, suggesting it may be safe.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4429719/

The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits ... Treatment of cancer cells with COH29 led to a dose-dependent S-phase arrest, induction of apoptosis, and cell death (Zhou et al., 2013).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02112565?tab=results

No Study Results Posted | NCT02112565 | RNR Inhibitor ... RNR Inhibitor COH29 in Treating Patients With Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy Exists.

4. faseb.onlinelibrary.wiley.com faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202101914RR

Ribonucleotide reductase holoenzyme inhibitor COH29 ... Overall, the aforementioned data reveal that COH29 could inhibit the invasion, migration, and EMT of the tested cancer cells.

5. sciencedirect.com sciencedirect.com/science/article/pii/S3050538025000286

Ribonucleotide reductases in cancer: Mechanisms, clinical ... This paper aims to comprehensively analyze the regulatory mechanisms of RNRs in cancer, evaluate the clinical efficacy and limitations of current RNRs ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02112565?tab=table

RNR Inhibitor COH29 in Treating Patients With Solid ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2014-00708

RNR Inhibitor COH29 in Treating Patients with Metastatic, ... This phase I trial studies the side effects and best dose of RNR Inhibitor COH29 in treating patients with solid tumors that have spread to other parts of the ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT189899

A phase I study to assess the safety, pharmacokinetics ... COH29 is an aromatically substituted thiazole compound that is a novel small molecule inhibitor of RNR activity, and exhibits unique mechanisms and target ...