Clinical trial NCT00098527: FR901228 in Treating Patients With Refractory Stomach Cancer or Gastroesophageal Junction Cancer
Official title: A Phase 2 Study of Single Agent Depsipeptide (FK228) in Gastric and Esophageal Cancers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adenocarcinoma of the Esophagus
Adenocarcinoma of the Stomach
Recurrent Esophageal Cancer
Recurrent Gastric Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-12-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Radiographic response rate (complete response & partial response)
timeFrame: Not Provided
Secondary outcomes:
measure: Progression-free survival (PFS) according to RECIST
timeFrame: Up to more than 6 months
measure: 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
timeFrame: Up to 12 months
measure: Correlation of changes in gene expression profile in dermal granulation tissue pre- and post-treatment with gene expression profile
timeFrame: Not Provided
measure: Correlation of wound vascular scores pre- and post-treatment with gene/protein changes
timeFrame: Not Provided
measure: Toxicity
timeFrame: Not Provided
measure: Changes in gene expression profile
timeFrame: At pre- and post-treatment
measure: Changes in levels of p21 and thymidine kinase expression, and tubulin acetylation using Western blotting
timeFrame: From baseline to 3 weeks
measure: Changes in gene expression profile in dermal granulation tissue
timeFrame: From baseline to up to 3 weeks
measure: Change in plasma and urine TGFB levels
timeFrame: At pre-and post-treatment
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Herbert Hurwitz
role: PRINCIPAL_INVESTIGATOR
References: