Depsipeptide/Flavopiridol Infusion for Cancers of the Lungs, Esophagus, Pleura, Thymus or Mediastinum
Status:
Terminated
Trial end date:
2013-05-20
Target enrollment:
Participant gender:
Summary
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.