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FR901228 in Treating Patients With Refractory Thyroid Cancer or Other Advanced Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: January 24, 2003   Last Updated: June 16, 2009   History of Changes
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00052767
  Purpose

RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of FR901228 in treating patients who have refractory thyroid cancer or other advanced cancer.


Condition Intervention Phase
Head and Neck Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: romidepsin
Phase I

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase I Trial of Romidepsin Given on Days One, Three and Five in Patients With Thyroid and Other Advanced Cancers

Resource links provided by NLM:


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

Estimated Enrollment: 56
Study Start Date: November 2002
Estimated Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of FR901228 (romidepsin) in patients with advanced cancer .
  • Determine the biologically effective dose of this drug in these patients.
  • Determine the effects of this drug on gene expression in these patients.
  • Determine whether this drug increases radioiodide uptake in patients with radioiodine-refractory non-medullary thyroid cancer.
  • Determine the effect of this drug on the expression of sodium-iodide symporter transporter in these thyroid cancer patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 3, and 5. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, an additional cohort of 10 patients with radioiodine-refractory non-medullary thyroid cancer are treated at that dose.

PROJECTED ACCRUAL: Approximately 3-56 patients (10 with radioiodine-refractory non-medullary thyroid cancer) will be accrued for this study within 17-21 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed cancer for which there is no known standard therapy capable of extending life expectancy (closed to accrual as of ½8/08)

    • No acute leukemia
  • Evaluable disease
  • No prior or concurrent CNS metastases
  • Thyroid cancer cohort (enrolled after the maximum tolerated dose for study drug has been determined):

    • Radioiodine (RAI)-refractory non-medullary thyroid cancer
    • Progressive disease after total or near-total thyroidectomy and RAI therapy
    • Evidence of no or minimal RAI uptake on RAI whole body scan
    • 24-hour urinary iodine no greater than 70 µg/day

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • More than 12 weeks

Hematopoietic

  • Absolute neutrophil count ≥1,000/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN

Renal

  • Creatinine ≤ 1.5 times ULN OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • Ejection fraction > 50% by echocardiogram or cardiac MRI (45% by MUGA)
  • No myocardial infarction within the past 12 months
  • No active coronary disease (e.g., angina) as defined by Canadian class II-IV
  • No QTc > 480 msec
  • No congenital long QT syndrome
  • No evidence of cardiac ischemia (e.g., ST depression ≥ 2 mm) as assessed by ECG
  • No NYHA class II-IV congestive heart failure
  • No history of sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, or cardiac arrest unless patient has an automatic implantable cardioverter defibrillator
  • No dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or other causes
  • No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 160 mm Hg or diastolic BP ≥ 95 mm Hg)
  • No cardiac arrhythmia requiring anti-arrhythmic medication other than beta blocker or calcium channel blocker
  • No Mobitz II second degree heart block unless patient has pacemaker

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study participation
  • HIV negative
  • No other serious uncontrolled medical illness
  • No uncontrolled infection
  • No other concurrent malignancies that have not been curatively treated
  • 24-hour urinary iodine values ≤ 150 μg/day

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin and 8 weeks for UCN-01)
  • No other concurrent chemotherapy, including topical treatments

Endocrine therapy

  • Concurrent corticosteroids for non-responding lesions allowed provided dose is stable

    • Corticosteroid therapy for cancer treatment may not be initiated after start of study

Radiotherapy

  • See Disease Characteristics
  • More than 3 months since prior RAI therapy*
  • More than 3 months since prior IV iodinated contrast or other large iodine loads (i.e., CT scan, amiodarone, or saturated solution of potassium iodide)*
  • Concurrent palliative localized external beam radiotherapy for metastatic cancer allowed provided treatment field does not include significant cardiac muscle and patient is responding to FR901228 (depsipeptide) NOTE: *Thyroid cancer cohort only

Surgery

  • See Disease Characteristics
  • Concurrent palliative surgery for metastatic cancer allowed provided patient is responding to FR901228

Other

  • At least 1 week since prior complementary and alternative medications (e.g., unprescribed dietary supplements or herbal remedies)
  • No concurrent complementary and alternative medications
  • No concurrent agents that are known to cause QTc prolongation
  • No concurrent digitalis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00052767

Locations
United States, Maryland
NCI - Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Clinical Trials Office - NCI - Center for Cancer Research     888-624-1937        
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
Sponsors and Collaborators
Investigators
Study Chair: Susan E. Bates, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000258737, NCI-03-C-0030, NCI-5483
Study First Received: January 24, 2003
Last Updated: June 16, 2009
ClinicalTrials.gov Identifier: NCT00052767     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
recurrent thyroid cancer

Study placed in the following topic categories:
Anti-Bacterial Agents
Thyroid Neoplasms
Head and Neck Neoplasms
Romidepsin
Endocrine System Diseases
Endocrinopathy
Thyroid Diseases
Recurrence
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Thyroid Neoplasms
Antineoplastic Agents
Therapeutic Uses
Head and Neck Neoplasms
Romidepsin
Endocrine System Diseases
Antibiotics, Antineoplastic
Pharmacologic Actions
Thyroid Diseases
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on September 11, 2009