Phase I Study of Weekly Intravenous PS-341 (Bortezomib) Plus Mitoxantrone in Patients With Advanced Androgen-Independent Prostate Cancer (AI-PCa)
Mitoxantrone is used to treat bone pain in advanced prostate cancer and inhibits many
proteins that the cancer cells need to multiply.
Bortezomib is a member of a new class of drugs that possess powerful and broad-spectrum
anti-tumor activity and inhibit many proteins that the cancer cells need to survive and
Pre-study testing will include brief physical examination, vital signs (weight, height,
temperature, pulse, respiratory and blood pressure), chest x-ray, EKG (test to measure the
electrical activity of the heart), echocardiogram, blood test, urine tests, and depending on
the stage of the disease, a CT scan and/or bone scan.
During treatment, the participants will receive one dose of Mitoxantrone combined with one
dose of Bortezomib every week for 4 weeks in a row followed by 2 weeks of rest; this is
called a course. If side effects are not too severe, Mitoxantrone and Bortezomib will be
infused rapidly into a vein while participants will be receiving normal saline ("salt in
water solution") at a rate of 100ml/hour. They will receive the salt solution the entire
time they are in the treatment area.
Participants will have their vital signs (temperature, pulse, breathing, blood pressure)
taken before and one hour after treatment. All side effects during course one will be
reviewed and, if no serious side effects took place, the participant may have additional
courses. A pill may be given by mouth every day to decrease the risk of clot formation or a
pill for diarrhea, nausea, and/or vomiting if the doctor believes that participants may need
Also during treatment, participants will have a complete physical examination by a physician
or their designated representative (such as a nurse or physician assistant) each week of
treatment. Bone Scan and/or CT Scan will be done if necessary. Participants will have
blood tests done every week during study. A special blood test, called the 20S proteosome,
will be done weekly during Cycles 1 and 2 to evaluate the activity of the drugs. Blood will
be collected before you receive treatment and then at 1-2 hours afterward. About 2 teaspoons
of blood will be collected each time for this. Bone scan, chest x-ray and/or CT scans will
be repeated during the study every other course.
Participants will be taken off study if the disease gets worse or intolerable side effects
occur. Side effects that are thought to be related to the study drug are renal failure
resulting in death, and a grade 3 rash requiring treatment with steroids that recurred with
The maximum amount of time that participants can remain on the study is 8 courses of
treatment. Long term follow-up of participants will include a phone call every 6 months.
This is an investigational study. Bortezomib has been approved by the FDA for
investigational use only. Mitoxantrone has been approved by the FDA for treatment of
symptoms in advanced prostate cancer. Only Mitoxantrone is commercially available. About 42
participants will take part in this study. All will be enrolled at M.D. Anderson .
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of Novantrone (Mitoxantrone) combined with PS-341 (Bortezomib)
A single-course MTD is defined as the dose level having mean posterior dose limiting toxicity probability closest to 25%.
Continual reassessment method, with each 5 week cycle
Arlene Siefker-Radtke, MD
UT M.D. Anderson Cancer Center
United States: Food and Drug Administration
|UT MD Anderson Cancer Center||Houston, Texas 77030|