Phase I Study of Weekly Intravenous PS-341 (Bortezomib) Plus Mitoxantrone
-Establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly mitoxantrone in combination with weekly PS-341 in patients with advanced AI-PCa.
- Evaluate the effect of bortezomib and mitoxantrone in combination on PSA levels among patients with baseline PSA levels >/=5 ng/mL who are treated near the maximum tolerated dose.
- Monitor the effect of escalating doses of bortezomib combined with mitoxantrone on selected parameters of clinical benefit (i.e. performance status, tumor-related symptoms, measurable disease response).
Drug: Mitoxantrone (Novantrone)
Drug: Bortezomib (PS-341)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Weekly Intravenous PS-341 (Bortezomib) Plus Mitoxantrone in Patients With Advanced Androgen-Independent Prostate Cancer (AI-PCa)|
- Maximum Tolerated Dose (MTD) of Novantrone (Mitoxantrone) combined with PS-341 (Bortezomib) [ Time Frame: Continual reassessment method, with each 5 week cycle ] [ Designated as safety issue: Yes ]A single-course MTD is defined as the dose level having mean posterior dose limiting toxicity probability closest to 25%.
- Activity of drug's biochemical target, the 20S proteasome, in peripheral blood white cells [ Time Frame: 7 Years ] [ Designated as safety issue: No ]
|Study Start Date:||March 2003|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: Bortezomib + Mitoxantrone
Bortezomib starting dose of 1.4 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15, and 22) over eight 5 week cycles.
Mitoxantrone starting dose of 3 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15 and 22) over eight 5 week cycles.
Drug: Mitoxantrone (Novantrone)
Starting dose of 3 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15 and 22) over eight 5 week cycles.Drug: Bortezomib (PS-341)
Starting Dose of 1.4 mg/m^2, four weekly intravenous injections (on Days 1, 8, 15, and 22) over eight 5 week cycles.
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 multiply.
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 it.
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 subsequent treatments.
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 .
Please refer to this study by its ClinicalTrials.gov identifier: NCT00059631
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Arlene Siefker-Radtke, MD||UT M.D. Anderson Cancer Center|