RNR Inhibitor COH29 in Treating Patients With Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy Exists
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|ClinicalTrials.gov Identifier: NCT02112565|
Recruitment Status : Recruiting
First Posted : April 14, 2014
Last Update Posted : September 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: RNR inhibitor COH29 Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
I. 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.
I. 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.
V. 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||June 13, 2016|
|Estimated Primary Completion Date :||November 2019|
|Estimated Study Completion Date :||November 2019|
Experimental: Treatment (RNR inhibitor COH29)
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
Other Name: pharmacological studies
- 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 [ Time Frame: Day 28 ]
- Changes in plasma biomarker expression levels [ Time Frame: Baseline to up to 30 days after completion of study treatment ]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.
- Pharmacokinetics of RNR inhibitor COH29 [ Time Frame: Pre-dose and 15 minutes, 30 minutes, 1, 2 , 3, 4, 6, 8, 24, and 168 hours post the day 1, course 1 dose ]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.
- Toxicities according to the National Cancer Institute (NCI) CTCAE v 4.0 [ Time Frame: Up to 30 days after completion of study treatment ]Toxicities will be tabulated by type and grade.
- Response rate [ Time Frame: Up to 30 days after completion of study treatment ]Response rate will be estimated in the overall population and 95% exact confidence intervals will be estimated.
- RR protein levels as assessed by automated quantitative analysis (AQUA) [ Time Frame: Baseline ]Will be summarized descriptively using means, median, standard deviation and range.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02112565
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Joseph Chao 626-471-9200 email@example.com|
|Principal Investigator: Joseph Chao|
|Principal Investigator:||Joseph Chao||City of Hope Medical Center|