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

July 27, 2010
November 30, 2012
July 2010
October 2011   (final data collection date for primary outcome measure)
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.
To compare the safety and tolerability of CUDC-101 at the MTD in subjects with advanced solid tumors (breast, gastric, head and neck, and liver 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.
Complete list of historical versions of study NCT01171924 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Head and Neck Cancer
  • Liver Cancer
  • Breast Cancer
  • Gastric Cancer
  • Non-Small Cell Lung Cancer
  • 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.
  • 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.
  • Experimental: Arm A: 5 days/week schedule
    Intervention: Drug: CUDC-101
  • Experimental: Arm B: 3 days/week schedule
    Intervention: Drug: CUDC-101
Lai CJ, Bao R, Tao X, Wang J, Atoyan R, Qu H, Wang DG, Yin L, Samson M, Forrester J, Zifcak B, Xu GX, DellaRocca S, Zhai HX, Cai X, Munger WE, Keegan M, Pepicelli CV, Qian C. CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity. Cancer Res. 2010 May 1;70(9):3647-56. doi: 10.1158/0008-5472.CAN-09-3360. Epub 2010 Apr 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
Not Provided
October 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01171924
CUDC-101-102
No
Curis, Inc.
Curis, Inc.
Not Provided
Not Provided
Curis, Inc.
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP