A Phase Ib Expansion Study Investigating the Safety, Efficacy, and Pharmacokinetics of Intravenous CUDC-101 in Subjects With Advanced Head and Neck, Gastric, Breast, Liver and Non-small Cell Lung Cancer Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Curis, Inc.
ClinicalTrials.gov Identifier:
NCT01171924
First received: July 27, 2010
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

This is a phase Ib open label, expansion study of CUDC-101 in patients with advanced head and neck, gastric, breast, liver, and non-small cell lung cancer 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 compare the safety and tolerability of CUDC-101 when administered at the maximum tolerated dose on either a 5 days/week schedule or a 3 days/week schedule.


Condition Intervention Phase
Head and Neck Cancer
Liver Cancer
Breast Cancer
Gastric Cancer
Non-Small Cell Lung Cancer
Drug: CUDC-101
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Open Label, Expansion Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Intravenous CUDC-101 in Subjects With Advanced Head and Neck, Gastric, Breast, Liver and Non-small Cell Lung Cancer Tumors

Resource links provided by NLM:


Further study details as provided by Curis, Inc.:

Primary Outcome Measures:
  • To compare the safety and tolerability of CUDC-101 in subjects with advanced solid tumors (breast, gastric, head and neck, liver, and non-small cell lung cancer) when administered at the MTD on either a 5 days/week schedule or 3 days/week schedule. [ Time Frame: 12-15 months ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be assessed in the two treatment arms and the incidence of adverse events, dose reductions, and patient compliance will be compared.


Secondary Outcome Measures:
  • To evaluate the efficacy of CUDC-101 in subjects with advanced and refractory solid tumors. [ Time Frame: 12-15 months ] [ Designated as safety issue: No ]
    Efficacy will be assessed using standard RECIST Criteria and the response rate and duration of responses will be compared between the two treatment arms.

  • To assess the pharmacokinetics of CUDC-101 in this patient population. [ Time Frame: 12-15 months ] [ Designated as safety issue: No ]
    Concentrations of CUDC-101 in blood and urine samples following CUDC-101 administration will be assessed and compared between the two treatment arms.

  • To evaluate pharmacodynamic biomarkers of CUDC-101 activity. [ Time Frame: 12-15 months ] [ Designated as safety issue: No ]
    The ability of CUDC-101 to modulate key target proteins including EGFR, HER2 and HDAC will be assessed in tumor biopsies and peripheral circulating cells.


Estimated Enrollment: 40
Study Start Date: July 2010
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: 5 days/week schedule Drug: CUDC-101
CUDC-101 administered as a 1 hour intravenous infusion at the maximum tolerated dose of 275 mg/m2 consecutively for 5 days on each 14 day cycle.
Experimental: Arm B: 3 days/week schedule Drug: CUDC-101
CUDC-101 administered as a 1 hour intravenous infusion at the maximum tolerated dose of 275 mg/m2 on Monday, Wednesday, Friday for three consecutive weeks of each 28 day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with histopathologically confirmed diagnosis of advanced breast, gastric, head and neck, liver and non-small cell lung cancer.

    • For subjects with non-small cell lung cancer only:

      • Most recent treatment must be erlotinib and subjects must have had a radiographic partial or complete response to treatment as defined by RECIST criteria and should be currently progressing after the documented response.
      • A documented mutation in EGFR exons 19 or 21
  • 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 use supplements 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.
  • 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. Subjects with liver cancer and hepatitis may be eligible.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01171924

Locations
United States, California
San Diego Pacific Oncology and Hematology Associates
Encinitas, California, United States, 92024
The Angeles Clinic and Research Institute
Los Angeles, California, United States, 90025
United States, Colorado
Mountain Blue Global Cancer Care
Wheat Ridge, Colorado, United States, 80033
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Texas
Mary Crowley Cancer Research Centers
Dallas, Texas, United States, 75230
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Curis, Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Curis, Inc.
ClinicalTrials.gov Identifier: NCT01171924     History of Changes
Other Study ID Numbers: CUDC-101-102
Study First Received: July 27, 2010
Last Updated: November 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Curis, Inc.:
Head and Neck Cancer
Liver Cancer
Breast Cancer
Gastric Cancer
Non-Small Cell Lung Cancer
EGFR
HDAC
Her2
CUDC-101

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Head and Neck Neoplasms
Liver Neoplasms
Lung Neoplasms
Stomach Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Stomach Diseases

ClinicalTrials.gov processed this record on April 21, 2014