RNR Inhibitor COH29 for Solid Tumors

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of RNR Inhibitor City of Hope 29 (COH29) in treating patients with solid tumors that are refractory to standard therapy or for which no standard therapy exists. COH29 may inhibit an enzyme called ribonucleotide reductase and may interfere with the ability of tumor cells to grow.

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.

What data supports the effectiveness of the drug COH29 for treating solid tumors?

Research shows that COH29, a drug that blocks a key enzyme needed for cancer cell growth, can reduce tumor growth in animal models and is effective against various cancer cell lines, including ovarian cancer and leukemia. It also overcomes resistance to other cancer drugs, making it a promising option for cancer treatment. ^{1 2 3 4 5}

Is COH29 safe for humans?

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. However, specific human safety data is not provided in the available research. ^{1 2 3 6 7}

Research Team

Vincent Chung

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

Absolute neutrophil count >= 1,500 cells/µL

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

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

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)

Treatment Details

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.

Participant Groups

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+

References

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

The Novel Ribonucleotide Reductase Inhibitor COH29 Inhibits DNA Repair In Vitro. [2018]

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

A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance. [2022]

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

Clofarabine Commandeers the RNR-α-ZRANB3 Nuclear Signaling Axis. [2021]

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

The RNA-Binding Protein HuR Confers Oxaliplatin Resistance of Colorectal Cancer By Upregulating CDC6. [2020]

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

Functional inhibition of the RNA-binding protein HuR sensitizes triple-negative breast cancer to chemotherapy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated β-catenin suppression. [2023]

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

A ribonucleotide reductase inhibitor with deoxyribonucleoside-reversible cytotoxicity. [2021]