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

NCT00728793 | Completed Phase 1

• 1 other identifier: CUDC-101-101
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Tumors

Keywords

Advanced Solid Tumors; EGFR; HDAC; Her2; Open-Label; Dose-Escalation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Number of patients that show a response (complete response or partial response) based on RECIST criteria.

  Study treatment period - approximately 12 months

• Plasma concentration of CUDC-101 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.

  Pre-treatment through Day 5 of cycle 1 - approximately 1 week

Interventions

CUDC-101 DRUG

Doses will be given by intravenous infusion over 1 hour on days 1-5 of each treatment cycle. Total treatment cycle duration will be 14 days. Additional treatment cycles will be administered until the subjects withdraws consent, experiences unacceptable toxicity, or if there is documented tumor progression.

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Curis, Inc.: lead

Study Sites (2)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

START (South Texas Accelerated Research Therapeutics)

San Antonio, Texas, 78229, United States

Location

Related Links

• Curis, Inc. Company Website

MeSH Terms

Conditions

Neoplasms

Interventions

7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide

Study Officials

• Anthony Tolcher, M.D.

  START (South Texas Accelerated Research Therapeutics)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 1, 2008
• First Posted: August 6, 2008
• Study Start: August 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: February 22, 2018

Record last verified: 2015-09

Locations

US (2)