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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00098527
First received: December 7, 2004
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Esophagus
Adenocarcinoma of the Stomach
Recurrent Esophageal Cancer
Recurrent Gastric Cancer
Drug: romidepsin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Single Agent Depsipeptide (FK228) in Gastric and Esophageal Cancers

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Radiographic response rate (complete response & partial response) [ Time Frame: Not Provided ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) according to RECIST [ Time Frame: Up to more than 6 months ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
  • Correlation of changes in gene expression profile in dermal granulation tissue pre- and post-treatment with gene expression profile [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Correlation of wound vascular scores pre- and post-treatment with gene/protein changes [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Not Provided ] [ Designated as safety issue: Yes ]
  • Changes in gene expression profile [ Time Frame: At pre- and post-treatment ] [ Designated as safety issue: No ]
  • Changes in levels of p21 and thymidine kinase expression, and tubulin acetylation using Western blotting [ Time Frame: From baseline to 3 weeks ] [ Designated as safety issue: No ]
  • Changes in gene expression profile in dermal granulation tissue [ Time Frame: From baseline to up to 3 weeks ] [ Designated as safety issue: No ]
  • Change in plasma and urine TGFB levels [ Time Frame: At pre-and post-treatment ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: October 2004
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (romidepsin)
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
Given IV
Other Names:
  • FK228
  • FR901228
  • Istodax
Other: laboratory biomarker analysis
Correlative studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098527

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Investigators
Principal Investigator: Herbert Hurwitz Duke University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00098527     History of Changes
Other Study ID Numbers: NCI-2012-02637, 6075-04-7R0, DUMC-6075-04-7R0, CDR0000398177, NCI-6351, U01CA099118
Study First Received: December 7, 2004
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Romidepsin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014