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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01171924
• Other study ID #: CUDC-101-102
• Status: Completed
• Phase: Phase 1
• First received: July 27, 2010
• Last updated: February 1, 2016
• Start date: July 2010
• Est. completion date: October 2011

Study information

• Verified date: February 2016
• Source: Curis, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Non-Small-Cell Lung
• Gastric Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Liver Cancer
• Liver Neoplasms
• Lung Neoplasms
• Non-Small Cell Lung Cancer
• Stomach Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Mary Crowley Cancer Research Centers	Dallas	Texas
United States	San Diego Pacific Oncology and Hematology Associates	Encinitas	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	Mountain Blue Global Cancer Care	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Curis, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	Safety and tolerability will be assessed in the two treatment arms and the incidence of adverse events will be compared.	12-15 months	Yes

External Links

•   Curis, Inc. Company Website