Loma Linda,
California
92357
Purpose:
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.
Study summary:
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.
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