Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

FR901228 in Treating Patients With Unresectable Recurrent or Metastatic Squamous Cell Carcinoma (Cancer) of the Head and Neck

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over NCI AECM-02025 NYWCCC-02025, 6335, NYWCCC-0402025S, NCI-6335, DFCI-04358, NCT00084682

Objectives

Primary

1. Determine the rate of disease control (i.e., achievement of complete response, partial response, or stable disease) in patients with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck treated with FR901228 (depsipeptide).

Secondary

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

Entry 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

Prior/Concurrent Therapy:

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 prior cumulative dose of doxorubicin more than 450 mg/m²
• No prior FR901228 (depsipeptide)
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy
• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• WBC ≥ 3,000/mm³
• 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

• QTc ≤ 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

Expected Enrollment

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

Outcomes

Disease control (complete response, partial response, or stable disease) as measured by RECIST criteria after 2 courses

Duration of response
Time to progression
Overall survival

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.

Haigentz M Jr, Adrien LR, Belbin TJ, et al.: Translational studies of depsipeptide (romidepsin, FK228), a histone deacetylase (HDAC) inhibitor, in patients with head and neck cancer. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-3524, 2007.

Haigentz M Jr, Kim M, Sarta C, et al.: Clinical and translational studies of depsipeptide (romidepsin), a histone deacetylase (HDAC) inhibitor, in patients with squamous cell carcinoma of the head and neck (SCCHN): New York Cancer Consortium trial P6335. [Abstract] J Clin Oncol 25 (Suppl 18): A-6065, 315s, 2007.

Trial Contact Information

Trial Lead Organizations

Albert Einstein Cancer Center at Albert Einstein College of Medicine

Missak Haigentz, MD, Protocol chair		Ph: 718-920-4826 Email: mhaigent@montefiore.org

U.S.A.
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Robert Haddad, MD	Ph:  617-632-3090
			Email: ehempel@partners.org
New York
	Bronx
	Albert Einstein Cancer Center at Albert Einstein College of Medicine
		Clinical Trials Office - Albert Einstein Cancer Center at Albert Einstein College of Medicine	Ph:  718-904-2730
			Email: aecc@aecom.yu.edu
	New York
	Mount Sinai School of Medicine
		Clinical Trials Office - Mount Sinai School of Medicine	Ph:  212-659-8050
	New York Weill Cornell Cancer Center at Cornell University
		Clinical Trials Office - New York Weill Cornell Cancer Center at Cornell University	Ph:  212-746-1848

Registry Information
Official Title		A Phase II Study Of Single Agent Depsipeptide (FK228; NSC 630176; IND51,810) In Patients With Unresectable Recurrent Or Metastatic Squamous Cell Carcinoma Of The Head And Neck
Trial Start Date		2004-04-02
Trial Completion Date		2006-02-21 (estimated)
Registered in ClinicalTrials.gov		NCT00084682
Date Submitted to PDQ		2004-04-02
Information Last Verified		2006-10-04
NCI Grant/Contract Number		CM17103, CA013330