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FR901228 in Treating Patients With Unresectable Recurrent or Metastatic Squamous Cell Carcinoma (Cancer) 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: June 11, 2013
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
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Salivary Gland Squamous Cell Carcinoma
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
Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Drug: romidepsin
Other: laboratory biomarker analysis
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 ]

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: 46
Study Start Date: April 2004
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
Other: laboratory biomarker analysis
Correlative studies

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:

  • Patients must have 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
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan
  • Patients may have received any number of prior systemic chemotherapy regimen for unresectable, recurrent or metastatic disease; chemotherapy must have been completed at least 4 weeks prior to entry into the study; patients treated previously with mitomycin C and nitrosoureas should have a therapy-free interval of at least 6 weeks duration prior to study entry; if patients have received doxorubicin in the past, their cumulative dose of doxorubicin should not be more than 450 mg/m^2; prior radiation therapy is allowed but must have been completed at least 4 weeks prior to study entry; 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
  • Patients must have 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
  • Patients should have a baseline EKG tracing; the screening EKG will be read by the local cardiologist, who will decide on inclusion or exclusion of the patient based on cardiac parameters; there should be no history of arrhythmias including atrial fibrillation, myocardial infarction or congestive heart failure; there should be no history of cardiac hypertrophy
  • Patients must not have a concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix; patients with prior malignancies who have been disease-free > 2 years are eligible
  • Patients must not have an active infection nor currently be receiving treatment for a recent infection
  • Patients must have recovered from the effects of any recent surgery
  • The effects of depsipeptide on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; a negative serum pregnancy test is required =< 2 weeks of randomization for women who are still menstruating
  • 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; because of the relatively small number of patients studied, biopsies will be required for participation; rarely, a patient may refuse post-treatment biopsy; in that event, the patient will be allowed to continue depsipeptide therapy if it is thought by the investigator that the patient is possibly deriving clinical benefit; the protocol can then possibly accrue additional patient/s to maintain adequate numbers of samples

Exclusion Criteria:

  • Patients who have had palliative chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • 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; also, patients may not be co-medicated with hydrochlorothiazide (HCTZ), an agent possibly associated with adverse events related to depsipeptide; patients who are taking HCTZ should have this medication stopped or switched to an acceptable potassium-conserving agent or other anti-hypertensive medication; patients taking warfarin concurrently with depsipeptide therapy will be monitored for elevations in INR, as a potential drug interaction exists
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because depsipeptide has unknown but potential risk for teratogenic or abortifacient effects; however, there is no evidence that depsipeptide itself is teratogenic or abortifacient; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with depsipeptide, breastfeeding should be discontinued if the mother is treated with depsipeptide
  • Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with depsipeptide
  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

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00084682     History of Changes
Other Study ID Numbers: NCI-2013-00027, MMC 04-02-025S, CDR0000365527, N01CM62204
Study First Received: June 10, 2004
Last Updated: June 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Laryngeal Neoplasms
Neoplasms, Unknown Primary
Oropharyngeal Neoplasms
Paranasal Sinus Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Neoplastic Processes
Nose Diseases
Nose Neoplasms
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Paranasal Sinus Diseases
Pathologic Processes
Pharyngeal Diseases
Pharyngeal Neoplasms
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Stomatognathic Diseases
Romidepsin
Antibiotics, Antineoplastic
Antineoplastic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014