Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Head & Neck Cancer
- Conditions
- Head and Neck Cancer
- Registration Number
- NCT01384799
- Lead Sponsor
- Curis, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
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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.
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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 desirable.
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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).
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Age ≥ 18 years
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ECOG performance < 2
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Life expectancy ≥ 3 months
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If female, neither pregnant nor lactating
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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 treatment.
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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.
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Serum magnesium and potassium within normal limits (may be supplemented to achieve normal values)
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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 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 treatment.
- 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 compounds.
- Central nervous system metastases.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method The number of participants with adverse events. 18-24 months Safety and tolerability will be assessed by evaluating the number of patients with adverse events
- Secondary Outcome Measures
Name Time Method The number of subjects disease free at the completion of the treatment period. 18-24 months To evaluate the efficacy of CUDC-101 in combination with cisplatin and radiation therapy by evaluating the number of subjects disease free at the completion of the treatment period.
The number of subjects disease free in the follow up period. 18-24 months To evaluate the efficacy of CUDC-101 in combination with cisplatin and radiation therapy by evaluating the number of subjects disease free in the follow up period.
Concentration of CUDC-101 in the blood over time. 18-24 months Pharmacokinetics will involve a determination of the concentration of CUDC-101 in the blood over time.
Number of circulating tumor cells pre treatment on Day -7 and 1 hour post treatment on Day -3. 18-24 months The ability of CUDC-101 to exert a biological effect on the tumor will be examined in pharmacodynamic samples.
Trial Locations
- Locations (7)
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Overton Brooks VA Medical Center
🇺🇸Shreveport, Louisiana, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States