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

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 2

Conditions: Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Recurrent Esophageal Cancer; Adenocarcinoma of the Esophagus

Treatments: Other: laboratory biomarker analysis; Drug: romidepsin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00098527

6075-04-7R0

NCI-2012-02637

U01CA099118 (U.S. NIH Grant/Contract)

NCI-6351

DUMC-6075-04-7R0

CDR0000398177

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Treatment (romidepsin)

Experimental group

Description:

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.

Treatment:

Drug: romidepsin

Other: laboratory biomarker analysis