Icotinib Hydrochloride in Treating Patients With Advanced Cancers
|ClinicalTrials.gov Identifier: NCT02033148|
Recruitment Status : Withdrawn (changes in study design by sponsor not acceptable for participating)
First Posted : January 10, 2014
Last Update Posted : November 5, 2014
|Condition or disease||Intervention/treatment||Phase|
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: icotinib hydrochloride Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
I. To determine the pharmacokinetic (PK) profiles of icotinib (icotinib hydrochloride) in patients with advanced cancers.
II. To determine the safety, tolerability and maximum tolerated dose (MTD) of icotinib in patients with advanced cancers.
I. To preliminarily assess the anti-tumor activity of icotinib in patients with advanced cancers.
II. To characterize the effect, if any, of icotinib on corrected QT interval using Bazett's formula (QTcB).
I. To evaluate single nucleotide polymorphisms in genes encoding for icotinib's target (epidermal growth factor receptor [EGFR]), putative transport protein (ATP-binding cassette, sub-family G [WHITE], member 1 [ABCG1]) and major metabolizing enzyme (cytochrome P450 3A4 [CYP3A4]) as well as other genes that may be found to be important in icotinib activity, and correlate these single nucleotide polymorphisms (SNPs) with clinical activity and toxicity.
OUTLINE: This is a dose-escalation study.
Patients receive icotinib hydrochloride orally (PO) twice daily (BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profile of Icotinib in Patients With Advanced Cancers|
|Study Start Date :||August 2014|
|Estimated Primary Completion Date :||June 2016|
Experimental: Treatment (icotinib hydrochloride)
Patients receive icotinib hydrochloride PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: icotinib hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Other Name: pharmacological studies
- MTD of icotinib hydrochloride, defined as the highest dose level at which =< 1 of 6 evaluable patients experiences a dose-limiting toxicity, as graded using NCI CTCAE version 4.0 [ Time Frame: 28 days ]Overall toxicity incidence as well as toxicity profiles by dose level, subject and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
- PK parameters of icotinib hydrochloride [ Time Frame: Cycle 1 only: Day -9 or Day -8: pre-dose, 0.5, 1, 2, 4, 6, 8, 24, and 48 hours; Day 8: pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 (Day 9 pre-dose) hours; Day 15: pre-dose trough ]Parameters include time to maximum concentration (Tmax), maximum concentration (Cmax), drug clearance (CL), half life (T 1/2), area under curve (AUC)0-infinity (inf), and AUC0-last measurable concentration (t) for the dosing interval following single and multiple dose administration.
- Objective tumor response, assessed using RECIST 1.1 [ Time Frame: Up to 30 days after last dose of study drug ]Objective tumor response will be tabulated overall (and by dose level if appropriate). Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in the cohorts (overall and by tumor group).
- Best response, defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) [ Time Frame: Up to 30 days after last dose of study drug ]Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in the cohorts (overall and by tumor group).
- Frequency of toxicities, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after last dose of study drug ]The frequency of toxicities will be tabulated by grade across all dose levels and cycles. The frequency of toxicities will also be tabulated for the dose estimated to be the MTD.
- Population pharmacokinetic model, developed utilizing pharmacokinetic timepoints collected [ Time Frame: Up to 30 days after last dose of study drug ]A population pharmacokinetic model will be used to estimate individual AUCs or CL of icotinib hydrochloride. AUC, as well as the observed Cmax, will then be tested for association changes polymorphism (SNP) information. If an observable trend exists among changes in any of the assessed biomarkers, a pharmacokinetic/pharmacodynamic model will be developed to evaluate the exposure-response relationship between the time-course of plasma exposure (e.g., AUC, Cmax) in relation to changes to these biomarkers. Demographic and clinical data will be utilized to assess interpatient variability.
- Icotinib hydrochloride-related genes [ Time Frame: Baseline ]Icotinib hydrochloride-related genes will be evaluated and their polymorphic variants will be correlated to clinical outcomes including response and toxicity. Fisher's exact tests will be used to compare the tumor response rates between the different tagged SNP subgroups. Kaplan-Meier curves and log rank tests will be used to compare the response rates distributions between the different tagged SNP subgroups. Correlative studies are only exploratory therefore no adjustments for multiple comparisons will be performed for the correlation of the polymorphisms with clinical outcomes.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02033148
|Principal Investigator:||Alex Adjei||Roswell Park Cancer Institute|