Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Head & Neck Cancer

Not Recruiting

Trial ID: NCT01384799


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.

Official Title

A Phase I Dose Escalation Study to Investigate the Safety and Pharmacokinetics of Intravenous CUDC-101 With Concurrent Cisplatin and Radiation Therapy in Subjects With Locally Advanced Head and Neck Cancer

Stanford Investigator(s)

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)


Inclusion Criteria:

   - Subjects with locally advanced, pathologically confirmed diagnosis of squamous cell
   carcinoma of the head and neck at the following sites: oral cavity, oropharynx,
   hypopharynx and larynx with either:

      - Stage IV p16 positive tumors and >10 pack-years smoking history.

      - Stage III/IV p16 negative tumors, regardless of smoking history.

   - At least evaluable disease; 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

   - Subjects enrolled in the MTD expansion cohort must have at least 1 tumor lesion that
   is suitable for repeat biopsy (pre- and post-CUDC-101 infusion).

   - 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); total bilirubin ≤ 1.5x ULN; AST/ALT ≤ 2
   x ULN.

   - Serum magnesium and potassium within normal limits (may be supplemented to achieve
   normal values)

   - Able to render informed consent and to follow protocol requirements.

Exclusion Criteria:

   - 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 prior to study treatment.

   - 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 within 6 months
   prior to study treatment.

   - Known history of stroke or cerebrovascular accident within 6 months prior to study

   - Symptomatic cardiac conduction abnormality within 12 months prior to study treatment.

   - 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

   - Central nervous system metastases.


radiation: Radiation Therapy

drug: CUDC-101

drug: Cisplatin

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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