A Phase 2 Study of Single Agent Depsipeptide (FK228) in Gastric and Esophageal Cancers

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the stomach or
gastroesophageal junction

- Measurable disease

- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
OR ≥ 10 mm by spiral CT scan

- Refractory* to at least 1, but no more than 3, of the following first-line agents:

- Fluoropyrimidine (e.g., capecitabine or fluorouracil)

- Taxane (e.g., paclitaxel or docetaxel)

- Platinum (e.g., carboplatin, cisplatin, or oxaliplatin)

- No known active brain metastases

- Treated brain metastases allowed provided metastases are stable off steroids for
≥ 30 days

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100%

- At least 3 months

- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

- Creatinine clearance ≥ 50 mL/min

- No congestive heart failure

- No New York Heart Association class III or IV heart disease

- No myocardial infarction within the past 6 months

- No ventricular arrhythmias requiring medication

- No angioplasty or vascular stenting within the past 3 months

- No unstable angina

- No left ventricular hypertrophy by EKG

- No known history of serious ventricular arrhythmia (e.g., ventricular tachycardia or
ventricular fibrillation ≥ 3 beats in a row)

- QTc < 500 msec

- LVEF > 40% by MUGA or echocardiogram

- No other significant cardiac disease

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Potassium ≥ 4.0 mmol/L (stable level with no change in supplementation within the
past 2 weeks)

- Magnesium ≥ 2.0 mg/dL (stable level with no change in supplementation within the past
2 weeks)

- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to study drug

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other uncontrolled illness

- Prior biological agents allowed

- No concurrent prophylactic filgrastim (G-CSF)

- No concurrent biologic therapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- No other concurrent chemotherapy

- More than 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy

- Prior targeted agents allowed

- No other prior or concurrent cytotoxic agents

- No other concurrent investigational agents

- No other concurrent anticancer therapy

- No concurrent medications causing QTc prolongation

- No concurrent potassium supplementation > 40 mg/day or magnesium supplementation > 1
g/week

- No concurrent hydrochlorothiazide

- No concurrent combination antiretroviral therapy for HIV-positive patients