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

Recurrent Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00098527
• Other study ID #: NCI-2012-02637
• Secondary ID: 6075-04-7R0DUMC-
• Status: Terminated
• Phase: Phase 2
• First received: December 7, 2004
• Last updated: July 1, 2013
• Start date: October 2004

Study information

• Verified date: July 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Esophagus
• Adenocarcinoma of the Stomach
• Esophageal Neoplasms
• Recurrent Esophageal Cancer
• Recurrent Gastric Cancer

Intervention

Drug:
• romidepsin
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic response rate (complete response & partial response)		Not Provided	No
Secondary	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	No
Secondary	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	Yes
Secondary	Correlation of changes in gene expression profile in dermal granulation tissue pre- and post-treatment with gene expression profile		Not Provided	No
Secondary	Correlation of wound vascular scores pre- and post-treatment with gene/protein changes		Not Provided	No
Secondary	Toxicity		Not Provided	Yes
Secondary	Changes in gene expression profile		At pre- and post-treatment	No
Secondary	Changes in levels of p21 and thymidine kinase expression, and tubulin acetylation using Western blotting		From baseline to 3 weeks	No
Secondary	Changes in gene expression profile in dermal granulation tissue		From baseline to up to 3 weeks	No
Secondary	Change in plasma and urine TGFB levels		At pre-and post-treatment	No