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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00084682
First received: June 10, 2004
Last updated: April 29, 2015
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: romidepsin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease Control (i.e., Achievement of Complete Response, Partial Response, or Stable Disease) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Tumor response was assessed every eight weeks by CT/MRI using RECIST (Response Evaluation Criteria in Solid Tumors) criteria


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to Progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    All time to event endpoints will be evaluated using Kaplan Meier estimates and survival curves will be generated based on these estimates.

  • Overall Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 14
Study Start Date: April 2004
Study Completion Date: March 2012
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (romidepsin)
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.
Drug: romidepsin
Given IV
Other Names:
  • FK228
  • FR901228
  • Istodax

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084682

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
Investigators
Principal Investigator: Missak Haigentz Montefiore Medical Center
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00084682     History of Changes
Other Study ID Numbers: NCI-2013-00027, MMC 04-02-025S, N01CM62204
Study First Received: June 10, 2004
Results First Received: April 29, 2015
Last Updated: April 29, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Laryngeal Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Pharyngeal Neoplasms
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Stomatognathic Diseases
Romidepsin
Antibiotics, Antineoplastic
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015