Breast Cancer, Gastric Cancer, Head and Neck Cancer, Liver Cancer, Non-Small Cell Lung Cancer
Conditions
Keywords
Head and Neck Cancer, Liver Cancer, Breast Cancer, Gastric Cancer, Non-Small Cell Lung Cancer, EGFR, HDAC, Her2, CUDC-101
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.
Interventions
DRUGCUDC-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.
Sponsors
Curis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 12-15 months | Safety and tolerability will be assessed in the two treatment arms and the incidence of adverse events will be compared. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: 5 Days/Week Schedule 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. | 23 |
| Arm B: 3 Days/Week Schedule 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. | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Arm A: 5 Days/Week Schedule | Total | Arm B: 3 Days/Week Schedule |
|---|---|---|---|
| Age, Continuous | 61.0 years | 63.0 years | 65.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 40 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 18 Participants | 31 Participants | 13 Participants |
| Region of Enrollment United States | 23 participants | 46 participants | 23 participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 13 Participants | 25 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 23 | 23 / 23 |
| serious Total, serious adverse events | 12 / 23 | 9 / 23 |
Outcome results
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.
Time frame: 12-15 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5 Days/Week Schedule | Number of Participants With Adverse Events | 23 participants |
| Arm B: 3 Days/Week Schedule | Number of Participants With Adverse Events | 23 participants |