Clinical trial NCT00728793: A Phase I Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of CUDC-101 in Patients With Advanced Solid Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumors
Keywords: Advanced Solid Tumors
EGFR
HDAC
Her2
Open-Label
Dose-Escalation
Lead sponsor: Curis, Inc.
Sponsor class: INDUSTRY
First posted: 2008-08-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: The highest dose level of CUDC-101 at which <33% of at least 6 or more subjects experiences a dose limiting toxicity.
timeFrame: Study treatment period - approximately 12 months
measure: The number of patients with adverse events.
timeFrame: Study treatment period - approximately 12 months
Secondary outcomes:
measure: Number of patients that show a response (complete response or partial response) based on RECIST criteria.
timeFrame: Study treatment period - approximately 12 months
measure: Plasma concentration of CUDC-101 over time from Day 1 through Day 6.
timeFrame: Approximately 1 week
measure: Measurement of epidermal growth factor receptor (EGFR) in archival tumor tissue, skin biopsies and tumor biopsies.
timeFrame: Pre-treatment through Day 5 of cycle 1 - approximately 1 week
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: San Antonio
country: United States
facility: START (South Texas Accelerated Research Therapeutics)
state: Texas
Study officials:
affiliation: START (South Texas Accelerated Research Therapeutics)
name: Anthony Tolcher, M.D.
role: PRINCIPAL_INVESTIGATOR
References: