FR901228 in Treating Patients With Refractory Stomach Cancer or Gastroesophageal Junction Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well FR901228 works in treating patients with refractory stomach cancer or gastroesophageal junction. Drugs used in chemotherapy, such as FR901228, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. FR901228 may also stop the growth of tumor cells by blocking some of the enzymes needed for their growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the radiographic response rate (complete response and partial response) in patients with refractory adenocarcinoma of the stomach or gastroesophageal junction treated with FR901228 (depsipeptide). SECONDARY OBJECTIVES: I. Determine the median time to progression and progression-free survival of patients treated with this drug. II. Determine the grade 3 and 4 toxic effects of this drug in these patients. OUTLINE: This is an open-label, 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. PROJECTED ACCRUAL: A total of 13-20 patients will be accrued for this study within 6.5-10 months.

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

Conditions
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Adenocarcinoma of the Esophagus, Adenocarcinoma of the Stomach, Recurrent Esophageal Cancer, Recurrent Gastric Cancer

Intervention / Treatment
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* Drug: romidepsin
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (romidepsin)<br>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. | Drug: romidepsin<br>* Given IV<br>* Other names: Istodax;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic response rate (complete response & partial response) |  | Not Provided | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) according to RECIST | The median time to progression and median PFS for all eligible patients, along with their CIs, will be reported. The Kaplan-Meier analysis approach may be used to summarize these time-to-event endpoints. | Up to more than 6 months | 
| Frequency of treatment related grade 1-4 toxicities and cardiac toxicities as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 |  | Up to 12 months | 
| Correlation of changes in gene expression profile in dermal granulation tissue pre- and post-treatment with gene expression profile |  | Not Provided | 
| Correlation of wound vascular scores pre- and post-treatment with gene/protein changes |  | Not Provided | 
| Toxicity |  | Not Provided | 
| Changes in gene expression profile |  | At pre- and post-treatment | 
| Changes in levels of p21 and thymidine kinase expression, and tubulin acetylation using Western blotting |  | From baseline to 3 weeks | 
| Changes in gene expression profile in dermal granulation tissue |  | From baseline to up to 3 weeks | 
| Change in plasma and urine TGFB levels |  | At pre-and post-treatment |