Depsipeptide/Flavopiridol Infusion for Cancers of the Lungs, Esophagus, Pleura, Thymus or Mediastinum

Stopped early · Phase 1

Conditions studied: Carcinoma, Small Cell, Carcinoma, Non-Small-Cell Lung, Esophageal Neoplasms, Mesothelioma

In brief

This study will test the safety and effectiveness of two experimental medicines - depsipeptide and flavopiridol - given together to treat cancers of the lung, esophagus, and pleura. It will determine the highest dose that these drugs can safely be given together and will test whether giving them together works better at shrinking tumors than giving either one alone. Patients 18 years of age and older with cancer of the lung, esophagus, or pleura, or other cancers that have spread to the lungs or pleura may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), x-rays and scans, pulmonary function tests, and a tumor biopsy (removal of a small piece of tumor tissue for microscopic examination). Participants are admitted to the hospital for treatment for approximately 10 days during each 28-day treatment cycle. Depsipeptide is infused through an arm vein or central venous catheter (tube placed in a large vein in the neck or chest) for 4 hours. When this infusion is complete, flavopiridol is infused over 72 hours. The dose of depsipeptide is increased four times over the period of the study with successive groups of patients, and flavopiridol is increased once to determine the maximum safe dose of giving these drugs together. Blood tests are done before and after each depsipeptide infusion and 3 more times for the next 24 hours, and at various times over 4 days during the flavopiridol infusion to evaluate the effects of the medicines. Samples are also drawn periodically throughout the treatment cycle to evaluate safety. Heart function is monitored with several EKGs before and during the depsipeptide doses. The drug has shown effects on EKG tracings, but does not appear to injure the heart muscle. Tumor biopsies are done before treatment begins and on the fifth day of the first treatment cycle. The biopsies may be done either in the operating room by passing a tube (bronchoscope) down the throat and into the lungs or in the Radiology Department using a thin needle put through the chest wall into the tumor. For the bronchoscopy, numbing medicine is sprayed into the back of the throat to reduce discomfort, and for the needle biopsy, the skin over the biopsy area is numbed. Optional repeat biopsies may be requested before the start of the second treatment cycle and on day 5 of that cycle. (The repeat biopsies are not required for participation in the study.) At the time of each tumor biopsy, a buccal mucosal biopsy is also done. This involves scraping a tongue depressor along the inside of the mouth to collect cells for examination. At the end of the first treatment cycle, patients return to NIH for evaluation with a physical examination, blood work, x-rays, and scans of the chest, abdomen, pelvis, and brain. Patients who are not experiencing significant drug side effects are offered a second cycle, exactly like the first. The two cycles complete one course of treatment, after which patients once again return to NIH for evaluation. Additional treatment cycles may be offered to patients whose tumors have shrunk or remained stable with therapy. Patients whose tumors have not responded to therapy or who have developed severe drug side effects are taken off the study.

Key facts

Study ID: NCT00094978
Run by: National Cancer Institute (NCI)
People needed: 23
Starts: 2004-10-25
Expected to finish: 2013-05-20
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 limited stage SCLC and operable NSCLC or operable esophageal cancer will be excluded.
Patients with potentially treatable pulmonary metastases from lymphomas or germ cell tumors will be excluded.
Patients who have received three or more systemic cytotoxic treatment regimens will be excluded due to possible cumulative marrow suppression.
Cardiac exclusion criteria, patients with known cardiac abnormalities such as:
Uncontrolled arrhythmias
History of serious ventricular arrhythmias not controlled by coronary artery bypass surgery.
Patients with a history of sustained VT, VF, Toursades de Pointes, or cardiac arrest who do not have an automatic implantable cardioverter defibrillator in place.
Congenital Long QT syndrome or QTc greater than 480 msec.
Patients with Mobitz II second degree block who do not have a pacemaker.
Patients with any cardiac arrhythmia requiring anti-arrhythmic medication other than a beta blocker or calcium channel blocker.
Patients in whom digitalis cannot be discontinued.
Decompensated heart failure (NYHA Class II or IV).
LVEF less than 50% by MUGA scan or echocardiogram.
Hypertrophic or restrictive cardiomyopathy from prior treatment of other causes and patients with left ventricular hypertrophy.
Uncontrolled hypertension (i.e. greater than or equal to160/95).
Myocardial infarction within one year of study.
Clinically significant active myocardial ischemia on the basis of nuclear imaging or angiography.
History of coronary artery disease (e.g. angina Canadian Class II-IV or positive stress imaging study).
Patients with other cardiac disease may be excluded at the discretion of the PI following consultation with cardiology.
Co-medication causing QTc prolongation (information at Appendix A and http://georgetowncert.org/gqdrugs_torsades.asp) unless a 5 half-life washout period has elapsed between discontinuing the drug and entering this study.
Patients with active intracranial and leptomeningeal metastases, as well as those requiring anticonvulsant medications or steroids to control cerebral edema will be excluded.
Patients with life expectancy less than three months will be excluded.
Patients with pulmonary embolism or deep venous thrombosis requiring anticoagulation within six months of protocol entry will be excluded.
Pregnant patients and nursing mothers will be excluded due to the unknown, potentially harmful effects of HDAC inhibitors and cdk inhibitors on fetal and early childhood development.
Patients with active infections will be excluded.

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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