Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer
Status:
Completed
Trial end date:
2009-11-01
Target enrollment:
Participant gender:
Summary
This study will examine the safety and effectiveness of treating adrenocortical cancer with
combination chemotherapy using doxorubicin, vincristine, and etoposide in addition to the
drugs mitotane and tariquidar and, when possible, surgery. Adrenocortical cancer cells have a
large amount of a protein called P-glycoprotein that "pumps" anti-cancer drugs out of the
cells, decreasing their effectiveness. Continuous infusions of doxorubicin, vincristine, and
etoposide may improve chemotherapy results by blocking the P-glycoprotein pump, as may use of
tariquidar, an experimental drug that is known to block the P-glycoprotein pump.
Patients 18 years of age and older with adrenocortical cancer that has recurred, spread, or
cannot be treated surgically may be eligible for this study. Candidates will be screened with
a medical history and physical examination; review of pathology slides; blood tests;
electrocardiogram (EKG); imaging tests, including computed tomography (CT) of the chest,
abdomen and pelvis; chest x-ray; and possibly a bone scan or other imaging tests needed to
evaluate the cancer, urine studies, and an echocardiogram. Also, a biopsy (removal of a small
sample of tumor tissue) may be required if a specimen is not available to confirm the cancer.
Participants will undergo the following tests and procedures:
- Tumor biopsy. Before starting chemotherapy, a small piece of tumor is removed to study
the P-glycoprotein pump and to determine the tumor genetics.
- Blood draw. Blood is drawn before treatment begins to establish baseline levels for
future blood tests.
- Central venous catheter placement. A specially trained physician places a plastic tube
into a major vein in the chest. The tube is used to give the study drugs and other
medications and to withdraw blood samples. It can stay in the body for months or be
removed after each treatment is completed. The tube placement is done under a local
anesthetic in the radiology department or operating room.
- Chemotherapy. Treatment cycles are 21 days. Doxorubicin, vincristine, and etoposide are
given through the central venous catheter by an infusion pump continuously over 96 hours
starting day 1 of each cycle. The dose of these drugs may be increased or decreased from
cycle to cycle, based on side effects. Mitotane is given in pill form starting day 1 of
cycle 1 and is taken every day throughout the entire study. The mitotane dose is
gradually increased as long as the side effects are tolerable. Tariquidar is given
through the central venous catheter as a 30-minute infusion on days 1 and 3 of every
cycle. The tariquidar dose remains the same throughout the study. Treatment will
continue for two cycles after all the cancer is gone, or until surgery is done to remove
some or all of the remaining cancer, or, if surgery is not an option, until the cancer
has grown to where it is defined as progressive disease.
- Nuclear scans. A nuclear scan is done before treatment begins and again on day 1 or day
3 of the first treatment cycle after administration of tariquidar to evaluate the P
glycoprotein response to treatment.
- Computed tomography (CT) scans. These scans are done every two treatment cycles to
follow disease progress.
- Surgery. Surgery to remove areas of cancer may be considered at any point during the
study (including before beginning treatment), if it is deemed beneficial. Treatment with
the study drugs will begin or resume after surgery. The length of treatment will depend
on the response to treatment before the surgery and on whether there is any cancer
remaining after the surgery.