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

Inclusion Criteria

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