FR901228 in Treating Patients With Previously Treated Unresectable Locally Advanced or Metastatic Colorectal Cancer

Phase II Trial of Depsipeptide (NSC-630176) in Colorectal Cancer Patients Who Have Received Either One or Two Prior Chemotherapy Regimens for Metastatic or Locally Advanced, Unresectable Disease

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: This phase II trial is studying how well FR901228 works in treating patients with unresectable locally advanced or metastatic colorectal cancer.

OBJECTIVES:

• Determine the confirmed response (complete and partial) in patients with previously treated unresectable locally advanced or metastatic colorectal cancer treated with FR901228 (depsipeptide).
• Determine the time to treatment failure and overall survival of patients treated with this drug.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.

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 8 weeks until disease progression and then every 3 months until 1 year after study entry and then every 6 months until 3 years after study entry.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 4-10 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer meeting 1 of the following criteria:

  • Locally advanced unresectable disease
  • Distant metastatic disease

• Measurable disease

• Previously treated with at least 1, but no more than 2, prior chemotherapy regimens for unresectable locally advanced or metastatic disease

  • May have included irinotecan or oxaliplatin
  • No more than 1 prior chemotherapy regimen (not oxaliplatin-based) for advanced or metastatic disease if previously treated with oxaliplatin-based adjuvant chemotherapy
  • No more than 1 prior chemotherapy regimen (not irinotecan-based) for advanced or metastatic disease if previously treated with irinotecan-based adjuvant chemotherapy

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• Bilirubin ≤ upper limit of normal (ULN)
• SGOT and SGPT ≤ 2.5 times ULN

Renal

• Creatinine ≤ ULN

Cardiovascular

• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past year
• No uncontrolled dysrhythmias
• No poorly controlled angina
• No prior serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No left ventricular hypertrophy
• QTc < 500 msec
• No other significant cardiac disease

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to FR901228

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent anticancer immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 28 days since prior chemotherapy and recovered
• No prior FR901228 (depsipeptide)
• No other concurrent anticancer chemotherapy

Endocrine therapy

• No concurrent anticancer hormonal therapy

Radiotherapy

• At least 28 days since prior radiotherapy and recovered
• No concurrent anticancer radiotherapy

Surgery

• At least 28 days since prior surgery and recovered

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent agent that causes QTc prolongation
• No concurrent hydrochlorothiazide
• No other concurrent investigational agents
• No other concurrent drugs that have histone deacetylase inhibitor activity (e.g., valproic acid)
• No other concurrent anticancer therapy