MDACC Study Summary ID02-227

Study Summary
No. ID02-227:.......Prostate......Arlene Siefker-Radtke......Genitourinary Medical Oncology

Study Summary Title



Study Summary Number:	ID02-227

Study Title:	Phase I Study of Weekly Intravenous PS-341 (bortezomib) Plus Mitoxantrone in Patients with Advanced Androgen-Independent Prostate Cancer (AI-PCa)

Physician

New Patient Referral



Name:	Arlene Siefker-Radtke	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Genitourinary Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2830 Contact us about clinical trials

General Information



Disease Group:	Prostate	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Weekly x 4 every 5 weeks cycle

Treatment Agents:	Mitoxantrone PS-341	Home Care:	None

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	None planned, outpatient treatment. If a patient is hospitalized for other reasons treatment may be given as inpatient. If a patient develops hypotension refractory to fluid replacement he may need inpatient hospitalization.


Description/ Intervention:	The goal of this clinical research study is to find the highest dose of Novantrone (Mitoxantrone) combined with PS-341 (Bortezomib) that can be given safely to participants. The activity of the drug's biochemical target, the 20S proteasome, will be measured in the peripheral blood white cells. The safety of Mitoxantrone and Bortezomib used together will also be studied.

Study Objectives / Outcomes

Primary Objective:

Establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), with degree of proteosome inhibition, of weekly mitoxantrone in combination with weekly bortezomib in patients with advanced AI-PCa.

Secondary objectives:

· 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).

Collect and/or store plasma, urine and tissue samples (i.e. prostate, bone marrow and / or lymph node) from consenting patients (optional procedures) for future studies (i.e., study the effect of the combination therapy on known targets of NFêB, growth factors for prostate cancer, and bone remodeling markers).

Study Status Information



Study Activation / Registration Date:	03/20/2003

IRB Review and Approval Date:	05/15/2002

Study Type:	Therapeutic

Recruitment Status:	Closed

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patient has given voluntary written informed consent before performance of any study-related procedure not part of standard medical care.

2) Patient has histologically-confirmed advanced and/or metastatic AI-PCa requiring anti-neoplastic treatment. Patients should continue on LHRH analog therapy throughout the study period, if this is their mode of androgen suppression therapy. Patients should have discontinued anti-androgen therapy for >/= than 4 weeks (for flutamide) or >/= 6 weeks (for bicalutamide and nilutamide).

3) Patient has progressive measurable or evaluable disease, defined as meeting at least one of the three criteria, described in protocol section 4.1.

4) Zubrod performance status of </= 2 (Appendix B).

5) Resting Left Ventricular Ejection Fraction (LEVF) >/= 50%.

6) Patient has all of the following pretreatment laboratory data within 14 days (except for serum testosterone which may be done within 28 days prior to registration) before the first study drug dose: Absolute neutrophil count (ANC) >/= 1,500/mm^3. Platelets >/= 100,000/mm^3. Hemoglobin >8.0 g/dL. Total bilirubin </=1.5 x the upper limit of normal (ULN). ALT or AST </= 2.5 x the ULN, or, if the patient has liver metastases, </= 5 x the ULN. Creatinine </= 2 mg/dL. Serum testosterone </= 50 ng/mL.

Exclusion Criteria:

1) Patient has received chemotherapy (including thalidomide or ketoconazole) within four weeks, nitrosoureas within six weeks, or antibody therapy within eight weeks of enrollment.

2) Patient has received radiation therapy or Samarium-153 within four weeks of enrollment, or Strontium-89 within 12 weeks of enrollment.

3) Patient has not recovered from all serious toxic effects of previous chemotherapy or radiation or antibody therapy.

4) Patient received treatment with flutamide within four weeks of enrollment or nilutamide or bicalutamide within six weeks of enrollment.

5) Patient has had any major surgery within four weeks of enrollment.

6) Patient has a history of allergic reactions to anti-diarrheal medications or anti-emetics suggested to be administered in conjunction with study drug (see Section 5.1.4.1).

7) Patient has a history of severe hypersensitivity reaction to mitoxantrone or other agents formulated with polysorbate 80.

8) Patients with significant atherosclerotic disease, as defined by: a) myocardial infarction within six months of enrollment, uncontrolled / unstable angina pectoris or electrocardiographic evidence of acute ischemia b) clinically significant ventricular arrhythmias, c) symptomatic congestive heart failure d) significant conduction abnormalities: 2nd or 3rd degree AV blocks, bifascicular block (defined as Left Anterior Hemiblock in the presence of Right Bundle Branch Block), e) claudication limiting activity and f) history of cerebrovascular events within the last year (including TIA)

9) Patients who have received > equivalent to 180 mg/m^2 of Doxorubicin cumulative dose.

10) Patients with diabetes mellitus requiring insulin, or those that have required pharmacologic intervention for diabetes mellitus for greater than 5 years

11) Patient has uncontrolled brain metastases or central nervous system disease.

12) Patient has >/= Grade 2 peripheral neuropathy (per NCI CTC v.2).

13) Patient has an uncontrolled intercurrent illness (e.g., active infection).

14) Patient has another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the patient's ability to provide informed consent or with the completion of treatment according to this protocol.

Links

Registration Number: NCT00059631
Study Information on Clinical Trials Registry (clinicaltrials.gov)