Phase I Trial of Bevacizumab, Metronomic Doxorubicin and Radiation Therapy for Resectable Soft Tissue Sarcoma
In order to determine if patients are eligible for this study patients will undergo some
screening procedures, including a medical history, physical examination, performance status,
assessment of tumor, chest CT scan, blood tests, urine test, electrocardiogram and
echocardiogram. Patients will also undergo blood tests and a tumor biopsy to look for
markers for your particular type of cancer.
If it is determined that patients are eligible to be in the study they will need to have a
central venous line (CVL), peripherally inserted central catheter (PICC), or portacath
placement. Doxorubicin administration requires a central venous line, peripherally inserted
central catheter (PICC) or portacath to be placed to allow continuous infusion of this drug.
Since the investigators are looking for the highest tolerable dose of the study drug,
bevacizumab, that can be administered safely without severe or unmanageable side effects in
participants that have sarcoma, not everyone who participates in this research study will
receive the same dose of the study drug. The dose patients get will depend on the number of
participants who have been enrolled in the study and how well they have tolerated their
doses. The dose of doxorubicin and radiation therapy will be the same for all subjects
throughout the study.
Bevacizumab will be given as an intravenous infusion (IV). The first infusion will take
about 90 minutes. All other bevacizumab infusions will take either 60 or 30 minutes, if
tolerated. The first infusion will be given on a Monday (excluding holidays). Patients will
receive the second infusion 2 weeks later and then every 2 weeks after that for a total of 3
Doxorubicin will be given as an intravenous infusion (IV). It will be given through a port
via an infusion pump about the size of a large wallet that can fit into a front-pack or
"fanny-pack" around their waist. This pump will be connected to their body. The nurses in
the infusion room will start the pump and disconnect it after 4 days. The first bolus
infusion take will be given 1-2 hours after their first bevacizumab infusion and will take
about 30 minutes. This will be followed by a continuous IV infusion of doxorubicin over 4
days. The first bolus infusion will be given on a Monday (excluding holidays) and the
continuous infusion will go until Thursday. Patients will receive a second bolus infusion
followed by a 4 day continuous infusion every week for 5 weeks.
Patients will begin radiation therapy after their first bevacizumab and doxorubicin infusion
on Monday (excluding holidays). Radiation therapy will be delivered five days per week
(Monday through Friday-excluding holidays) over a period of 6 weeks. This is done as an
outpatient procedure. Each 2-week period will be considered a separate treatment cycle.
Patients will be treated with radiation therapy for a maximum of 3 cycles (6 weeks).
The following tests and procedures will be done during the study during weeks 2, 4 and 6 and
before surgery: a medical history, physical examination, performance status, blood tests,
urine tests and assessment for any side effects. Patients will have additional CT scans of
their chest and tumor before surgery. An ECG will be repeated at this time.
A surgeon will evaluate the tumor by reviewing radiologic studies before study treatment to
determine if surgical removal is possible. After patients complete study treatment with
radiation therapy and bevacizumab, a surgeon will repeat the evaluation of the tumor by
reviewing radiologic studies to determine if surgical removal is still possible. Patients
will have surgery 6-7 weeks after they finish radiation therapy.
Patients will have additional radiation therapy if the research doctor thinks that some
cancer cells may have been left in their body in the area where the tumor was removed. The
radiation may be given while patients are in surgery or about two weeks after the surgery.
This will be determined by the surgeon and or radiation oncologist.
Patients will be in this research study for about 3 months. After the last dose of the study
drug the investigators would like to keep track of their medical condition for 10 years. The
investigators would like to do this by calling patients by telephone once a year to see how
they are doing. Keeping in touch with them and checking their condition every year helps the
investigators look at the long term effects of the research study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine MTD of bevacizumab+doxorubicin+radiation
To determine the maximum tolerated dose of bevacizumab when administered concurrently with metronomic doxorubicin and radiation therapy for resectable intermediate and high-grade soft tissue sarcomas
Edwin Choy, MD
Massachusetts General Hospital
United States: Food and Drug Administration
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|