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

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Curis, Inc.

ClinicalTrials.gov Identifier:

NCT01384799

First received: June 17, 2011

Last updated: April 18, 2013

Last verified: April 2013

History of Changes

Tracking Information
First Received Date ^ICMJE	June 17, 2011
Last Updated Date	April 18, 2013
Start Date ^ICMJE	June 2011
Estimated Primary Completion Date	June 2013 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: May 1, 2012)	To establish the safety and tolerability of CUDC-101 when administered in combination with concurrent cisplatin and radiation in subjects with locally advanced head and neck cancers. [ Time Frame: 18-24 months ] [ Designated as safety issue: Yes ] Safety and tolerability will be assessed by the number of participants with adverse events and will determine the maxiumum tolerated dose of CUDC-101 in combination with cisplatin and radiation.
Original Primary Outcome Measures ^ICMJE (submitted: June 28, 2011)	To establish the safety and tolerability of CUDC-101 when administered in combination with concurrent cisplatin and radiation in subjects with locally advanced human papillomavirus negative head and neck cancers. [ Time Frame: 18-24 months ] [ Designated as safety issue: Yes ] Safety and tolerability will be assessed by the number of participants with adverse events and will determine the maxiumum tolerated dose of CUDC-101 in combination with cisplatin and radiation.
Change History	Complete list of historical versions of study NCT01384799 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: April 26, 2012)	To evaluate the efficacy of CUDC-101, cisplatin and radiation combination therapy. [ Time Frame: 18-24 months ] [ Designated as safety issue: No ] Efficacy of CUDC-101 will be determined by the number of subjects disease free at the completion of the treatment period and the number of subjects remaining disease free in the follow up period. To assess the pharmacokinetics of CUDC-101. [ Time Frame: 18-24 months ] [ Designated as safety issue: No ] Pharmacokinetics will involve a determination of the concentration of CUDC-101 in the blood over time. To evaluate the pharmacodynamic effects of CUDC-101. [ Time Frame: 18-24 months ] [ Designated as safety issue: No ] The ability of CUDC-101 to exert a biological effect on the tumor will be examined in pharmacodynamic samples.
Original Secondary Outcome Measures ^ICMJE (submitted: June 28, 2011)	To evaluate the efficacy of CUDC-101, cisplatin and radiation therapy combination in subjects with locally advanced human papillomavirus negative head and neck cancers. [ Time Frame: 18-24 months ] [ Designated as safety issue: No ] Efficacy of CUDC-101 will be determined by the number of subjects disease free at the completion of the treatment period and the number of subjects remaining disease free in the follow up period. To assess the pharmacokinetics of CUDC-101 in this patient population. [ Time Frame: 18-24 months ] [ Designated as safety issue: No ] Pharmacokinetics will involve a determination of the concentration of CUDC-101 in the blood over time. To evaluate tumor markers for response associated with CUDC-101, cisplatin and radiation activity. [ Time Frame: 18-24 months ] [ Designated as safety issue: No ] The ability of CUDC-101 to exert a biological effect on the tumor via alteration of target proteins will be examined in biopsies obtained both pre and post treatment.
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Head & Neck Cancer
Official Title ^ICMJE	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
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 Provided
Study Type ^ICMJE	Interventional
Study Phase	Phase 1
Study Design ^ICMJE	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Condition ^ICMJE	Head and Neck Cancer
Intervention ^ICMJE	Drug: CUDC-101 CUDC-101 will be administered as a 1 hour intravenous infusion three times per week for a one week run-in (week -1) and then as part of the combination treatment on weeks 1-7. If the 225 mg/m2 dose is tolerated in the first cohort, the dose will be increased to 275 mg/m2. If the 225 mg/m2 dose is not tolerated, the dose will be decreased to 175 mg/m2. If 175 mg/m2 is not tolerated the dose will be further decreased to 150 mg/m2. Drug: Cisplatin Cisplatin will be administered intravenously at a dose of 100 mg/m2 on days 2, 23 and 44 of the seven week combination treatment course. Other Names: cisplatinum CDDP Platinol Radiation: Radiation Therapy The initial target volume encompassing the gross and subclinical disease sites will receive 2.0 Gy per fraction, five fractions per week. The gross disease sites will receive 70 Gy in 35 fractions over seven weeks and the subclinical disease sites will receive 56 Gy in 35 fractions, again over seven weeks.
Study Arm (s)	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Active, not recruiting
Estimated Enrollment ^ICMJE	22
Estimated Completion Date	June 2013
Estimated Primary Completion Date	June 2013 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	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 desirable. 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 treatment. 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 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.
Gender	Both
Ages	18 Years and older
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	United States

Administrative Information
NCT Number ^ICMJE	NCT01384799
Other Study ID Numbers ^ICMJE	CUDC-101-103
Has Data Monitoring Committee	No
Responsible Party	Curis, Inc.
Study Sponsor ^ICMJE	Curis, Inc.
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Curis, Inc.
Verification Date	April 2013
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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