RNR Inhibitor COH29 in Treating Patients With Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy Exists

NCT02112565 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: 14023NCI-2014-00708
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of RNR inhibitor COH29, defined as the dose level with no more than 1 dose limiting toxicity (DLT) in the first 6 patients at a dose level below a dose level with DLT in 2 of 6 patients, graded according to CTCAE version 4.0

  Day 28

Secondary Outcomes (5)

• Changes in plasma biomarker expression levels

  Baseline to up to 30 days after completion of study treatment

• Pharmacokinetics of RNR inhibitor COH29

  Pre-dose and 15 minutes, 30 minutes, 1, 2 , 3, 4, 6, 8, 24, and 168 hours post the day 1, course 1 dose

• Toxicities according to the National Cancer Institute (NCI) CTCAE v 4.0

  Up to 30 days after completion of study treatment

• Response rate

  Up to 30 days after completion of study treatment

• RR protein levels as assessed by automated quantitative analysis (AQUA)

  Baseline

Study Arms (1)

Treatment (RNR inhibitor COH29)

EXPERIMENTAL

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.

Drug: RNR inhibitor COH29; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

RNR inhibitor COH29 DRUG

Given PO

Also known as: COH29, ribonucleotide reductase holoenzyme inhibitor COH29

Treatment (RNR inhibitor COH29)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (RNR inhibitor COH29)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (RNR inhibitor COH29)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have the ability to understand and the willingness to sign a written informed consent
• Life expectancy of greater than 3 months by physician assessment
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) solid tumor that is metastatic, unresectable, progressive, or recurrent, and for which standard curative or palliative measures do not exist or are no longer effective
• Patients must have measurable or evaluable disease
• Patients must not have received prior chemotherapy or radiation for \< 4 weeks prior to start of study treatment
• Patients may be entered if they have received prior radiation therapy involving =\< 30% of the bone marrow; any prior radiation therapy must have been administered \>= 4 weeks prior to start of study treatment and the patient must be recovered from the acute toxic effects of the treatment prior to start of study treatment
• Patients may be enrolled with a history of treated brain metastases that are clinically stable for \>= 4 weeks prior to start of study treatment
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; women of child-bearing age will undergo urine pregnancy testing prior to study enrollment; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• Active breast-feeding is also not allowed on study enrollment
• Leukocytes \>= 3,000 cells/µL
• Absolute neutrophil count \>= 1,500 cells/µL
• Platelets \>= 100, 000 cells/µL
• Total bilirubin =\< 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN; AST/ALT =\< 5 x ULN if liver metastasis is present

You may not qualify if:

• Patients may not be receiving any other investigational agents; use of over-the-counter herbal medications will also be excluded
• 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
• Patients unable or unwilling to swallow pills
• Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease or heart block, or uncontrolled congestive heart failure
• Patients with a history of noninfectious pneumonitis will be excluded during the dose-escalation phase of the trial
• Patients, who in the opinion of the investigator and another independent party, may not be able to adhere to the safety monitoring requirements of the study

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Study Officials

• Vincent Chung

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: April 14, 2014
• Study Start: June 13, 2016
• Primary Completion: November 23, 2018
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (1)