AzTrials
AzTrials

Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT02112565

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

A Phase 1 study testing RNR inhibitor COH29, laboratory biomarker analysis and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RNR inhibitor COH29, laboratory biomarker analysis and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
9 Jan 2017to 12 May 2027
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 18Show fewer
  • 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
  • Serum creatinine =< 1.5 mg/dL or a measured creatinine clearance >= 50 mL/min
  • Prothrombin time (PT)/international normalized ratio (INR)/ activated partial thromboplastin time (aPTT) =< 1.5 x ULN
  • Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only)

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase I, Dose-Escalation, Safety and Tolerability Study of COH29 in Patients With Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose of COH29 (ribonucleotide reductase [RNR] inhibitor COH29) and recommended dose for further phase II testing.

II. To determine the pharmacokinetics of COH29.

SECONDARY OBJECTIVES:

  1. To characterize the safety and tolerability of COH29 by assessing toxicities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

II. To characterize any clinical activity of COH29 via objective tumor response.

III. To assess pharmacodynamic response of COH29 on ribonucleotide reductase (RR) and poly-adenosine diphosphate-ribose polymerase (PARP) activity in peripheral blood mononuclear cells (PBMCs).

IV. To explore baseline RRM2 tumor protein expression as a potential correlative marker for COH29 response.

  1. To explore measurement of plasma cytokeratin 18 (CK18) as a surrogate pharmacodynamic marker of COH29 antitumor activity.

OUTLINE: This is a dose escalation study.

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

After completion of study treatment, patients are followed up for 30 days.

Being tested
RNR inhibitor COH29, laboratory biomarker analysis, pharmacological study

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RNR inhibitor COH29Drug

    Also called COH29, ribonucleotide reductase holoenzyme inhibitor COH29

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT02112565
Study groupRoleWhat they receive
Treatment (RNR inhibitor COH29)ExperimentalPatients receive RNR inhibitor COH29 PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: RNR inhibitor COH29; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Day 28

Secondary outcomes (5)

  1. Changes in plasma biomarker expression levels

    Descriptive statistics and graphical displays will be used to summarize levels of plasma CK18, dNTP pools, gamma-H2AX, and PAR expression at each time point and evaluate changes between pre- and post-treatment measurements. A paired t-test will be used to determine if there is a statistically significant change.

    Measured: Baseline to up to 30 days after completion of study treatment

  2. Pharmacokinetics of RNR inhibitor COH29

    COH29 levels in plasma will be quantitated using a validated High Performance Liquid Chromatography (HPLC) tandem mass spectrometry (LC-MS/MS) method. Summary statistics of the pharmacokinetic parameters for the population will be derived from the parameters obtained in individual patients.

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

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

    Toxicities will be tabulated by type and grade.

    Measured: Up to 30 days after completion of study treatment

  4. Response rate

    Response rate will be estimated in the overall population and 95% exact confidence intervals will be estimated.

    Measured: Up to 30 days after completion of study treatment

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

    Will be summarized descriptively using means, median, standard deviation and range.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2014 (estimated)
  2. Study start9 Jan 2017
  3. Primary completion23 Nov 2018
  4. Study completion12 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02112565
Sponsor's protocol ID
14023
Other IDs
NCI-2014-00708, 14023
Status last verified
Oct 2026
First submitted
9 Apr 2014
Last updated
20 Oct 2026
Results posted
No
Data monitoring committee
Yes

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in