Depsipeptide to Treat Thyroid and Other Advanced Cancers

NCT00048334 | Completed Phase 1

• 2 other identifiers: 03003003-C-0030
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neoplasms

Keywords

Histone Acetylation; Cancer

Outcome Measures

Primary Outcomes (1)

• To define the MTD of romidepsin when administered on a multi-daly regimen of days 1, 3, and 5.

Secondary Outcomes (1)

• To correlate laboratory assays of the molecular effects of romidepsin with the administered dose.

Interventions

Depsipeptide, FR901228, FK228 DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologic or cytologic confirmation of cancer (excluding acute leukemia) for which there is no known standard therapy capable of extending life expectancy.
• Patients must:
• Be age greater than or equal to 18 years.
• Have evaluable disease.
• Have a performance status of ECOG 0-2.
• Have no serious or intercurrent illness that can not be medically controlled and have a have a life expectancy of greater than 12 weeks.
• Give written informed consent.
• Be willing to return to National Cancer Institute for follow-up.
• Female patients of childbearing potential must have a negative pregnancy test within 1 week and must use effective contraception (hormonal or barrier methods) while being treated on protocol.
• \. Laboratory values:
• Within 7 days prior to registration: absolute neutrophil count greater than or equal to 1000/microL, platelets greater than or equal to l00,000/microL, bilirubin (total and direct) less than or equal to 1.5x upper limit of normal, and AST less than or equal to 3x upper limit of normal, creatinine less than or equal to1.5x upper limit of normal, or documented creatinine clearance of greater than or equal to 60mL/min.
• Within 4 weeks of registration: ejection fraction of greater than 50% by echocardiogram or cardiac MRI, or 45% by MUGA scan.
• \. Criteria for cohort of patients with RAI refractory non-medullary thyroid cancer to be enrolled after the MTD has been defined:
• Non-medullary thyroid carcinoma.
• progressive disease following total or near-total thyroidectomy and RAI therapy.

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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity. J Antibiot (Tokyo). 1994 Mar;47(3):301-10. doi: 10.7164/antibiotics.47.301.

  PMID: 7513682 BACKGROUND

• Ueda H, Manda T, Matsumoto S, Mukumoto S, Nishigaki F, Kawamura I, Shimomura K. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice. J Antibiot (Tokyo). 1994 Mar;47(3):315-23. doi: 10.7164/antibiotics.47.315.

  PMID: 8175484 BACKGROUND

• Ueda H, Nakajima H, Hori Y, Goto T, Okuhara M. Action of FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum no. 968, on Ha-ras transformed NIH3T3 cells. Biosci Biotechnol Biochem. 1994 Sep;58(9):1579-83. doi: 10.1271/bbb.58.1579.

  PMID: 7765477 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

Depsipeptides; romidepsin

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Richard L Piekarz, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 29, 2002
• First Posted: October 30, 2002
• Study Start: October 26, 2002
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: December 12, 2019

Record last verified: 2014-01-07

Locations

US (1)