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Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Primary Purpose

Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
romidepsin
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IV Squamous Cell Carcinoma of the Hypopharynx

Eligibility Criteria

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

Inclusion Criteria: histologically or cytologically confirmed squamous cell cancer of the head and neck (MedDRA code 90002024), excluding nasopharyngeal primaries, which is unresectable or metastatic; the disease must be incurable with surgery or radiation therapy; the tumor should preferably be present at the primary site, and it must be accessible to planned biopsy methods Measurable disease by RECIST, May have received any number of prior systemic chemotherapy regimen for unresectable, recurrent or metastatic disease; if the only site of measurable disease is a previously irradiated area, the patient must have documented progressive disease or biopsy-proven residual carcinoma; persistent disease after radiotherapy must be biopsy-proven at least 8 weeks after the completion of radiotherapy Life expectancy of greater than 3 months Normal organ and marrow function as defined by the following labs performed =< 2 weeks of study entry: Leukocytes ≥ 3,000/uL Absolute Neutrophil Count ≥ 1,500/uL Hemoglobin ≥ 10 gm% Platelets ≥ 100,000/uL Total Bilirubin =< 1.5 X upper normal institutional limit AST(SGOT)/ALT(SGPT) =< 2.5 X upper normal institutional limits Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal PT/PTT =< 1.1X upper normal institutional limits Calcium within normal institutional limits CPK, Troponin within normal institutional limits Uric Acid within normal institutional limits Ability to understand and the willingness to sign a written informed consent document; in addition to consent for the therapy, patients must give consent to required pre- and post-therapy blood and tissue samples; Exclusion Criteria: Patients should not have had prior therapy with depsipeptide and may not be receiving any other investigational agents or drugs known to have histone deacetylase inhibitor activity such as sodium valproate Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events Significant cardiac disease including congestive heart failure that meets New York Heart Association (NYHA) class III and IV definitions (see Appendix II), history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias, or poorly controlled angina History of serious ventricular arrhythmia (VT or VF, > 3 beats in a row), QTc > 500 msec, or LVEF < 40% Patients may not be co-medicated with an agent that causes QTc prolongation; - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements Not pregnant or lactating History of HIV infection

Sites / Locations

  • Dana-Farber Cancer Institute
  • Montefiore Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (romidepsin)

Arm Description

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Disease Control (i.e., Achievement of Complete Response, Partial Response, or Stable Disease)
Tumor response was assessed every eight weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions as assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable disease (SD) was defined as having no evidence of response (CR or PR) as best response to therapy, and no evidence of disease progression (appearance of new lesions or >/= 30% increase in target lesions) at 8 weeks.

Secondary Outcome Measures

Duration of Response
Time to Progression
All time to event endpoints will be evaluated using Kaplan Meier estimates and survival curves will be generated based on these estimates.
Overall Survival
All time to event endpoints will be evaluated using Kaplan Meier estimates and survival curves will be generated based on these estimates. One and two-year survival and median survival time (if attained) will be estimated and reported with 95% confidence limits. If the sample sizes are sufficient, subgroup analysis based on baseline factors will be performed using the log rank test to compare survival curves.

Full Information

First Posted
June 10, 2004
Last Updated
February 11, 2021
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00084682
Brief Title
Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Official Title
A Phase II Study of Single Agent Depsipeptide (FK228; NSC 630176; IND 51,810) in Patients With Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial is studying how well FR901228 works in treating patients with unresectable recurrent or metastatic squamous cell carcinoma (cancer) of the head and neck. Drugs used in chemotherapy such as FR901228 work in different ways to stop tumor cells from dividing so they stop growing or die.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the rate of disease control (i.e., achievement of complete response, partial response, or stable disease) of the single agent depsipeptide in patients with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck. SECONDARY OBJECTIVES: I. To evaluate the duration of response, time to progression, and overall survival for patients with incurable head and neck cancer treated with depsipeptide. TERTIARY OBJECTIVES: I. To determine the extent of histone hyperacetylation in peripheral blood mononuclear cells (PBMCs) as a readout of depsipeptide activity before and after depsipeptide administration, to correlate this activity with observed histone hyperacetylation in tumor and mucosal cells, and to correlate extent of depsipeptide activity with tumor response. II. To determine depsipeptide-induced changes in the gene expression profile of tumor cells from biopsies of accessible tumor tissue and of mucosal cells from transepithelial oral brush biopsies using cDNA microarrays containing 28,000 clones, and to correlate these changes with extent of histone hyperacetylation observed in PBMCs and tumor tissues. III. To determine depsipeptide-induced changes in methylation of candidate genes in tumor cells and oral mucosa epithelia. IV. To demonstrate altered expression of signaling and cell cycle-related proteins in tumor tissue in response to depsipeptide. OUTLINE: This is a multicenter study. Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Oropharynx

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (romidepsin)
Arm Type
Experimental
Arm Description
Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
romidepsin
Other Intervention Name(s)
FK228, FR901228, Istodax
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Disease Control (i.e., Achievement of Complete Response, Partial Response, or Stable Disease)
Description
Tumor response was assessed every eight weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions as assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable disease (SD) was defined as having no evidence of response (CR or PR) as best response to therapy, and no evidence of disease progression (appearance of new lesions or >/= 30% increase in target lesions) at 8 weeks.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Duration of Response
Time Frame
Up to 2 years
Title
Time to Progression
Description
All time to event endpoints will be evaluated using Kaplan Meier estimates and survival curves will be generated based on these estimates.
Time Frame
Up to 2 years
Title
Overall Survival
Description
All time to event endpoints will be evaluated using Kaplan Meier estimates and survival curves will be generated based on these estimates. One and two-year survival and median survival time (if attained) will be estimated and reported with 95% confidence limits. If the sample sizes are sufficient, subgroup analysis based on baseline factors will be performed using the log rank test to compare survival curves.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: histologically or cytologically confirmed squamous cell cancer of the head and neck (MedDRA code 90002024), excluding nasopharyngeal primaries, which is unresectable or metastatic; the disease must be incurable with surgery or radiation therapy; the tumor should preferably be present at the primary site, and it must be accessible to planned biopsy methods Measurable disease by RECIST, May have received any number of prior systemic chemotherapy regimen for unresectable, recurrent or metastatic disease; if the only site of measurable disease is a previously irradiated area, the patient must have documented progressive disease or biopsy-proven residual carcinoma; persistent disease after radiotherapy must be biopsy-proven at least 8 weeks after the completion of radiotherapy Life expectancy of greater than 3 months Normal organ and marrow function as defined by the following labs performed =< 2 weeks of study entry: Leukocytes ≥ 3,000/uL Absolute Neutrophil Count ≥ 1,500/uL Hemoglobin ≥ 10 gm% Platelets ≥ 100,000/uL Total Bilirubin =< 1.5 X upper normal institutional limit AST(SGOT)/ALT(SGPT) =< 2.5 X upper normal institutional limits Creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal PT/PTT =< 1.1X upper normal institutional limits Calcium within normal institutional limits CPK, Troponin within normal institutional limits Uric Acid within normal institutional limits Ability to understand and the willingness to sign a written informed consent document; in addition to consent for the therapy, patients must give consent to required pre- and post-therapy blood and tissue samples; Exclusion Criteria: Patients should not have had prior therapy with depsipeptide and may not be receiving any other investigational agents or drugs known to have histone deacetylase inhibitor activity such as sodium valproate Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events Significant cardiac disease including congestive heart failure that meets New York Heart Association (NYHA) class III and IV definitions (see Appendix II), history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias, or poorly controlled angina History of serious ventricular arrhythmia (VT or VF, > 3 beats in a row), QTc > 500 msec, or LVEF < 40% Patients may not be co-medicated with an agent that causes QTc prolongation; - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements Not pregnant or lactating History of HIV infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Missak Haigentz
Organizational Affiliation
Montefiore Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22748449
Citation
Haigentz M Jr, Kim M, Sarta C, Lin J, Keresztes RS, Culliney B, Gaba AG, Smith RV, Shapiro GI, Chirieac LR, Mariadason JM, Belbin TJ, Greally JM, Wright JJ, Haddad RI. Phase II trial of the histone deacetylase inhibitor romidepsin in patients with recurrent/metastatic head and neck cancer. Oral Oncol. 2012 Dec;48(12):1281-8. doi: 10.1016/j.oraloncology.2012.05.024. Epub 2012 Jun 28.
Results Reference
result

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Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

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