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

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CUDC-101
Cisplatin
Radiation Therapy
Sponsored by
Curis, Inc.
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford Cancer Center
  • University of Colorado Cancer Center
  • Overton Brooks VA Medical Center
  • Massachusetts General Hospital
  • Henry Ford Health System
  • Fox Chase Cancer Center
  • Vanderbilt University

Outcomes

Primary Outcome Measures

The number of participants with adverse events.
Safety and tolerability will be assessed by evaluating the number of patients with adverse events

Secondary Outcome Measures

The number of subjects disease free at the completion of the treatment period.
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.
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.
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.
The ability of CUDC-101 to exert a biological effect on the tumor will be examined in pharmacodynamic samples.

Full Information

First Posted
June 17, 2011
Last Updated
February 15, 2018
Sponsor
Curis, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01384799
Brief Title
Phase I Study of CUDC-101 With Cisplatin and Radiation in Subjects With Head & Neck Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Curis, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
CUDC-101
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
cisplatinum, CDDP, Platinol
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
The number of participants with adverse events.
Description
Safety and tolerability will be assessed by evaluating the number of patients with adverse events
Time Frame
18-24 months
Secondary Outcome Measure Information:
Title
The number of subjects disease free at the completion of the treatment period.
Description
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.
Time Frame
18-24 months
Title
The number of subjects disease free in the follow up period.
Description
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.
Time Frame
18-24 months
Title
Concentration of CUDC-101 in the blood over time.
Description
Pharmacokinetics will involve a determination of the concentration of CUDC-101 in the blood over time.
Time Frame
18-24 months
Title
Number of circulating tumor cells pre treatment on Day -7 and 1 hour post treatment on Day -3.
Description
The ability of CUDC-101 to exert a biological effect on the tumor will be examined in pharmacodynamic samples.
Time Frame
18-24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Overton Brooks VA Medical Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71101
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
01911
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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