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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00728793
Recruitment Status : Completed
First Posted : August 6, 2008
Last Update Posted : February 21, 2018
Information provided by (Responsible Party):
Curis, Inc.

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.

Condition or disease Intervention/treatment Phase
Tumors Drug: CUDC-101 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : August 2008
Actual Primary Completion Date : April 2010
Actual Study Completion Date : April 2010

Intervention Details:
  • Drug: CUDC-101
    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.

Primary Outcome Measures :
  1. The highest dose level of CUDC-101 at which <33% of at least 6 or more subjects experiences a dose limiting toxicity. [ Time Frame: Study treatment period - approximately 12 months ]
    The maximum tolerated dose is the highest dose level at which <33% of at least 6 or more subjects experiences a dose limiting toxicity.

  2. The number of patients with adverse events. [ Time Frame: Study treatment period - approximately 12 months ]
    The number of patients with adverse events will be assessed to determine the safety and tolerability of CUDC-101.

Secondary Outcome Measures :
  1. Number of patients that show a response (complete response or partial response) based on RECIST criteria. [ Time Frame: Study treatment period - approximately 12 months ]
    To evaluate the efficacy of CUDC-101 in subjects with advanced and refractory solid tumors, responses based on RECIST criteria will be evaluated.

  2. Plasma concentration of CUDC-101 over time from Day 1 through Day 6. [ Time Frame: Approximately 1 week ]
    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.

  3. Measurement of epidermal growth factor receptor (EGFR) in archival tumor tissue, skin biopsies and tumor biopsies. [ Time Frame: Pre-treatment through Day 5 of cycle 1 - approximately 1 week ]
    Measurement of EGFR to evaluate pharmacodynamic biomarkers of CUDC-101 activity.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT00728793

United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Texas
START (South Texas Accelerated Research Therapeutics)
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Curis, Inc.
Principal Investigator: Anthony Tolcher, M.D. START (South Texas Accelerated Research Therapeutics)

Additional Information:
Responsible Party: Curis, Inc. Identifier: NCT00728793     History of Changes
Other Study ID Numbers: CUDC-101-101
First Posted: August 6, 2008    Key Record Dates
Last Update Posted: February 21, 2018
Last Verified: September 2015

Keywords provided by Curis, Inc.:
Advanced Solid Tumors