A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of CUDC-101 in Patients With Advanced Solid Tumors

A Phase I Open-Label, Multiple Dose, Sequential Dose Escalation Study to Investigate the Safety and Pharmacokinetics of Intravenous CUDC-101 in Subjects With Advanced and Refractory Solid Tumors

This is a phase I, open-label, dose-escalation study of CUDC-101 in patients with advanced and refractory solid tumors. CUDC-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor Type 2(Her2) and histone deacetylase (HDAC). The study is designed to establish the safety, including the maximum tolerated dose, the pharmacokinetics, and the anti-tumor activity of CUDC-101.

Study Overview

• Status: Completed
• Conditions: Tumors
• Intervention / Treatment: Drug: CUDC-101

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • START (South Texas Accelerated Research Therapeutics)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with advanced, refractory solid tumors and a histopathologically confirmed diagnosis
• Subjects must have no further standard of care options or have refused standard therapy
• Measurable or evaluable disease
• Age ≥ 18 years
• ECOG performance < 2
• Life expectancy ≥ 3 months
• If female, neither pregnant or lactating
• If of child bearing potential, must use adequate birth control
• Absolute neutrophil count ≥ 1,500/µL; platelets ≥ 100,000/µL;
• Creatinine ≤ 1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60mL/min/1.73m2
• Total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2.5x ULN. In subjects with documented liver metastases, the AST/ALT may be ≤ 5x ULN
• Prothrombin time ≤1.5x ULN, unless receiving therapeutic anticoagulation
• Serum magnesium and potassium within normal limits (may be supplement to achieve normal values)
• Subjects with brain metastases are eligible if controlled on a stable dose ≤ 10mg prednisone/day or its equivalent dose of steroids
• Able to render informed consent and to follow protocol requirements.

Exclusion Criteria:

• Anticancer therapy within 4 weeks of study entry. Prostate cancer subjects on LHRH hormonal therapy may be enrolled and continue on this therapy.
• Use of investigational agent(s) within 30 days of study entry
• History of cardiac disease with a New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF), myocardial infarction (MI) or unstable angina in the past 6 months prior to Day 1 of treatment, serious arrhythmias requiring medication for treatment.
• Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C.

• The following are permitted but should be used with caution and other suitable agents used if possible:

  • Subjects receiving concomitant medications metabolized by CYP 3A4 and CYP 2D6
  • CYP3A4 inducers
  • CYP3A4 inhibitors
  • Warfarin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The highest dose level of CUDC-101 at which <33% of at least 6 or more subjects experiences a dose limiting toxicity.	The maximum tolerated dose is the highest dose level at which <33% of at least 6 or more subjects experiences a dose limiting toxicity.	Study treatment period - approximately 12 months
The number of patients with adverse events.	The number of patients with adverse events will be assessed to determine the safety and tolerability of CUDC-101.	Study treatment period - approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients that show a response (complete response or partial response) based on RECIST criteria.	To evaluate the efficacy of CUDC-101 in subjects with advanced and refractory solid tumors, responses based on RECIST criteria will be evaluated.	Study treatment period - approximately 12 months
Plasma concentration of CUDC-101 over time from Day 1 through Day 6.	To assess the pharmacokinetics of CUDC-101 in this patient population, plasma concentration of CUDC-101 will be measured over time from Day 1 through Day 6.	Approximately 1 week
Measurement of epidermal growth factor receptor (EGFR) in archival tumor tissue, skin biopsies and tumor biopsies.	Measurement of EGFR to evaluate pharmacodynamic biomarkers of CUDC-101 activity.	Pre-treatment through Day 5 of cycle 1 - approximately 1 week

Collaborators and Investigators

• Sponsor: Curis, Inc.
• Investigators: Principal Investigator: Anthony Tolcher, M.D., START (South Texas Accelerated Research Therapeutics)

Publications and helpful links

Helpful Links

• Curis, Inc. Company Website

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: August 1, 2008
• First Submitted That Met QC Criteria: August 1, 2008
• First Posted (Estimate): August 6, 2008

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: February 15, 2018
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: EGFR; Advanced Solid Tumors; Dose-Escalation; Her2; Open-Label; HDAC
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CUDC-101-101