RATIONALE: Drugs used in chemotherapy such as FR901228 work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of FR901228 in treating patients who have unresectable recurrent or metastatic squamous cell carcinoma (cancer) of the head and neck.

Condition	Treatment or Intervention	Phase
Head and Neck Cancer	Drug: FR901228  Procedure: chemotherapy	Phase II

OBJECTIVES: Primary

• Determine the response rate in patients with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck treated with FR901228.

Secondary

• Determine the duration of response, time to disease progression, and overall survival of patients treated with this drug.
• Correlate the extent of drug activity with tumor response in these patients.
• Determine changes in the gene expression profile of tumor cells and buccal mucosa cells in patients treated with this drug.
• Determine changes in methylation of candidate genes in tumor cells and buccal mucosa epithelia in patients treated with this drug.
• Determine altered expression of signaling and cell cycle-related proteins in tumor tissue in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive FR901228 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.

PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
• Unresectable recurrent or metastatic disease
• No nasopharyngeal primaries
• Incurable with surgery or radiotherapy
• Measurable disease
• At least 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan
• Must have disease progression or biopsy proven residual carcinoma if the only site of measurable disease is in a previously irradiated field
• Persistent disease after radiotherapy must be biopsy proven at least 8 weeks after the completion of radiotherapy
• Accessible to planned biopsy methods
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,000/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• PT and PTT ≤ 1.1 times ULN

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min
• Calcium normal
• Uric acid normal

Cardiovascular

• QT ≤ 500 msec
• CPK and troponin normal
• No significant cardiac disease
• No history of cardiac hypertrophy
• No history of serious ventricular arrhythmias (ventricular tachycardia or ventricular fibrillation > 3 beats in a row)
• No atrial fibrillation
• No uncontrolled dysrhythmias
• No poorly controlled angina
• No myocardial infarction within the past year
• No New York Heart Association class III or IV congestive heart failure

Other

• Potassium ≥ 4 mmol/L
• Magnesium ≥ 2 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active or ongoing infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation the would preclude study compliance
• No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy
• No concurrent biologic agents

Chemotherapy

• More than 4 weeks since prior chemotherapy, including palliative chemotherapy, (6 weeks for mitomycin or nitrosoureas) and recovered
• No more than 1 prior systemic chemotherapy regimen for unresectable recurrent or metastatic disease
• No prior cumulative dose of doxorubicin more than 450 mg/m^2
• No prior chemotherapy for recurrent disease if patient received primary, curative-intent radiotherapy
• No prior FR901228
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior palliative radiotherapy
• More than 6 months since prior primary, curative-intent radiotherapy (with or without chemotherapy)
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• No concurrent therapy for infection
• No concurrent agents that cause QTc prolongation
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent hydrochlorothiazide
• No other concurrent drugs with histone deacetylase inhibitor activity (e.g., sodium valproate)
• No other concurrent antineoplastic or investigational agents

Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States; Recruiting
      Mount Sinai School of Medicine, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Missak Haigentz, MD,  Study Chair,  Albert Einstein Cancer Research Center   

Study ID Numbers:  CDR0000365527; NYWCCC-02025; NYWCCC-0402025S; NCI-6335
Record last reviewed:  September 2004
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084682
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08