Clinical trial NCT01171924: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Cancer
Liver Cancer
Breast Cancer
Gastric Cancer
Non-Small Cell Lung Cancer
Keywords: Head and Neck Cancer
Liver Cancer
Breast Cancer
Gastric Cancer
Non-Small Cell Lung Cancer
EGFR
HDAC
Her2
CUDC-101
Lead sponsor: Curis, Inc.
Sponsor class: INDUSTRY
First posted: 2010-07-29
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 12-15 months
Secondary outcomes:
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: San Diego Pacific Oncology and Hematology Associates
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Wheat Ridge
country: United States
facility: Mountain Blue Global Cancer Care
state: Colorado
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References:
citation: 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.