Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Human Papillomavirus Negative Head and Neck Cancer
Phase: Phase 1
Diagnosis: Head and Neck Cancer
NCT ID: NCT01384799
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-103
This is a phase I dose escalation study of CUDC-101 in combination with concurrent cisplatin and radiation therapy in patients with locally advanced head and neck cancer. 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, tolerability and maximum tolerated dose (MTD) of CUDC-101 when administered in combination with concurrent cisplatin and radiation over an 8-week treatment course, consisting of a one week run-in period of CUDC-101 administered alone, followed by seven weeks of combination treatment with CUDC-101, cisplatin and radiation therapy.
Massachusetts General Hospital
Lori Wirth, MD,
Massachusetts General Hospital
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
- Subjects with stage III/IV, locally advanced, pathologically confirmed diagnosis of
human papillomavirus negative squamous cell carcinoma of the head and neck.
- At least evaluable disease and one measurable site of disease according to RECIST
(Version 1.1) criteria (at least 10 mm for conventional CT/MRI or spiral CT scan) is
- Age ≥ 18 years
- ECOG performance < 2
- Life expectancy ≥ 3 months
- If female, neither pregnant nor lactating
- If of child bearing potential, must use adequate birth control throughout the
participation in the treatment phase and for 60 days following the last study
- Absolute neutrophil count ≥ 1,800/µL; platelets ≥ 100,000/µL; hemoglobin ≥ 8.0 g/dL,
creatinine ≤ 1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥
60mL/min; total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2 x ULN ; prothrombin time and INR
≤1.5x ULN, unless receiving therapeutic anticoagulation
- Serum magnesium and potassium within normal limits (may be supplemented to achieve
- Able to render informed consent and to follow protocol requirements.
- Prior radiotherapy to the region of the study cancer or adjacent anatomical sites, or
> 25% of marrow-bearing area.
- Prior chemotherapy for the current indication.
- Prior therapy that specifically and directly targets EGFR, HER2 or HDAC.
- Use of investigational agent(s) within 30 days of study entry
- Primary tumor site of nasopharynx, sinuses, or salivary gland.
- 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.
- Patients with prolonged QTc Interval >450 msec.
- Acquired Immune Deficiency Syndrome (AIDS) or known infection with human
immunodeficiency virus (HIV). Testing is not required.
- Known history of gastrointestinal bleeding, ulceration, or perforation
- Known history of stroke or cerebrovascular accident in the past 6 months prior to Day
1 of treatment.
- Symptomatic conduction abnormality within the past 12 months.
- Prior history of hearing impairment.
- Known history of renal disease or ongoing renal impairment
- Any uncontrolled condition (such as active systemic infection, diabetes,
hypertension), which in the opinion of the investigator, could affect the subjects
participation in the study.
- Prior allergic reaction to cisplatin, carboplatin or other platinum-containing
- Symptomatic central nervous system metastases.