Depsipeptide to Treat Thyroid and Other Advanced Cancers

Completed · Phase 1

Conditions studied: Neoplasms

In brief

This phase I study will evaluate the experimental drug Romidepsinin patients with advanced cancer. The study will: 1) determine how well patients tolerate Romidepsin; 2) measure blood levels of Romidepsin during treatment; 3) analyze the cellular and molecular effects of the drug; and 4) determine if Romidepsin can shrink tumors. Romidepsin has been shown to kill cancer cells growing in the laboratory and to shrink tumors in animals with various tumor types. In preliminary studies, several patients with a type of lymphoma and one patient with kidney cancer responded to treatment. Patients 18 years of age and older with advanced cancer (excluding acute leukemia) may be eligible for this study. Candidates are screened with a medical history and physical examination, x-rays and CT scans, and blood and urine tests. Patients with thyroid cancer may also have magnetic resonance imaging (MRI). This test uses a magnetic field instead of x-rays to obtain images or body organs and tissues. Participants receive three infusions of Romidepsin administered through an intravenous line over 4 hours on days 1, 3 and 5 of a 21-day treatment cycle. The intravenous line is a catheter (plastic tube) placed in a vein and may be a peripheral line, inserted in a vein in the arm, or a central line, in which the tube is placed under the skin of the chest or neck into a major vein. Patients are hospitalized for the first 6 days of the first cycle to monitor heart rate. Those who tolerate the treatment well may continue as an outpatient. In addition to drug therapy, participants undergo the following procedures: * Blood tests: Small amounts of blood are drawn frequently during the first five days of treatment to measure Romidepsin levels and to see how the body uses and excretes the drug. A heparin lock (an indwelling device to keep the vein open) may be put in the vein to prevent the need for repeated needle sticks. * Biopsies (removal of a small sample of tumor tissue): Tumors that are accessible may be biopsied at the start of the study and at different times during treatment. Biopsies are done no more than three times per cycle, and no more than nine biopsies are done within a year. The samples are examined for the effects of Romidepsin on proteins that control the way cells divide and stay alive. * Apheresis: This procedure is done to collect white blood cells and cancer cells for research. Blood is collected through a needle in an arm vein and directed into a machine that separates it into its components by centrifugation (spinning). The white cells are removed and the red cells are returned to the patient through the same needle or through another needle in the other arm. * Scans and x-rays: Imaging studies are usually done before starting treatment. Some of them are repeated at every 2 cycles (6 weeks), and some at the end of the patient's participation in the study. The tests may include chest x-rays, plain x-rays of affected bones, CT scans of the chest, abdomen, and pelvis, bone scans, and a MUGA scan (special X-ray of the heart) or echocardiogram (ultrasound of the heart) to test heart function before and during the study. MRI or positron emission tomography (PET) scans may also be done to detect tumors. PET scans use a small amount of a radioactive substance injected into a vein. The radioactivity is detected by a special camera during scanning to detect cancer cells. * Other tests include an electrocardiogram (recording of the electrical activity of the heart) before and after each dose of depsipeptide. Eye exams are done if there are vision changes or if the doctor recommends an eye test.

Key facts

Study ID: NCT00048334
Run by: National Cancer Institute (NCI)
People needed: 28
Starts: 2002-10-26
Expected to finish: 2010-04-01
Last updated by the study team: 2019-12-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients with unconfirmed diagnosis will be excluded.
Prior or concurrent malignancies that have not been curatively treated.
Current or previous CNS metastasis.
Chemotherapy within 4 weeks, 6 weeks for nitrosoureas or mitomycin C, and 8 weeks for UCN-01.
HIV seropositivity.
Pregnant or breast-feeding patients.
Uncontrolled infection.
Patients with the following cardiac risk factors will be excluded from the study:
Patients with known cardiac abnormalities such as: Congenital long QT syndrome and -QTc interval greater than 480 milliseconds
Patients who have had a myocardial infarction within 12 months of study entry.
Patients who have active coronary artery disease, e.g. angina as defined by Canadian Class II-IV
Patients with an ECG recorded at screening showing evidence of cardiac ischemia (ST depression of greater than or equal to 2 mm).
Any patient in whom coronary artery disease is suspected should be referred for a cardiology consultation and if active myocardial ischemia is demonstrated, the patient should be excluded. If a noninvasive imaging study is equivocal, it may be necessary to proceed to coronary angiography.
Patients with congestive heart failure that meets NYHA Class II to IV definitions and/or ejection fraction less than 45% by MUGA scan or less than 50% by echocardiogram and/or MRI.
Patients with a history of sustained VT, VF, Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD). Patients with a history of arrhythmia should have Holter monitoring and evaluation by cardiology.
Patients with dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or other causes (in doubt, see ejection fraction criteria above). Patients with left ventricular hypertrophy should be discussed with the Principal Investigator or Study Chairman.
Patients with uncontrolled hypertension, i.e. SBP greater than or equal to 160 mm Hg or DBP greater than or equal to 95 mm Hg.
Patients with cardiac arrhythmia requiring anti-arrhythmic medication other than beta blocker or calcium channel blocker. Patients in whom digitalis cannot be discontinued are excluded from study.
Patients with Mobitz II second degree heart block who do not have a pacemaker. Patients with first degree or Mobitz I second degree heart block, bradyarrhythmias or sick sinus syndrome require Holter monitoring and evaluation by cardiology.
Patients with other cardiac disease may be excluded at the discretion of the PI following consultation with cardiology.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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