Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Bortezomib and Mitoxantrone in Treating Patients With Advanced or Metastatic Androgen-Independent Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	Not specified	NCI, Pharmaceutical / Industry	MDA-ID-02227 MILLENNIUM-MDA-ID-02227, NCT00082680

Special Category: SPORE trial

Objectives

Primary

1. Determine the dose-limiting toxicity and maximum tolerated dose (MTD) of bortezomib and mitoxantrone in patients with advanced or metastatic androgen-independent prostate cancer.

Secondary

1. Determine the degree of proteasome inhibition in peripheral blood of patients treated with this regimen.
2. Correlate the effect of this regimen on prostate-specific antigen (PSA) levels with the degree of proteasomal inhibition in the blood of patients with baseline PSA levels ≥ 5 ng/mL who are treated near the MTD.
3. Determine the effect of this regimen on selected parameters of clinical benefit (i.e., performance status, tumor-related symptoms, and measurable disease response) in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed androgen-independent prostate cancer
  • Advanced or metastatic disease



• Requires antineoplastic therapy



• Progressive measurable or evaluable disease



• Testosterone ≤ 50 ng/dL



• No uncontrolled brain metastases



• No CNS disease

Prior/Concurrent Therapy:

Biologic therapy

• More than 8 weeks since prior antibody therapy and recovered

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No prior cumulative doxorubicin dose ≥ 180 mg/m²

Endocrine therapy

• At least 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide)
• Patients receiving luteinizing hormone-releasing hormone analog therapy for androgen suppression should continue this therapy throughout study participation

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• More than 4 weeks since prior samarium Sm 153 lexidronam pentasodium
• More than 12 weeks since prior strontium chloride Sr 89

Surgery

• More than 4 weeks since prior major surgery

Patient Characteristics:

Age

• Not specified

Performance status

• Zubrod 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin > 8.0 g/dL
• Platelet count ≥ 100,000/mm³

Hepatic

• ALT or AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 2 mg/dL

Cardiovascular

• LVEF ≥ 50% at rest
• None of the following significant atherosclerotic diseases:
  • Myocardial infarction within the past 6 months
  • Uncontrolled or unstable angina pectoris
  • Acute ischemia by ECG
  • Clinically significant ventricular arrhythmias
  • Symptomatic congestive heart failure
  • Any of the following significant conduction abnormalities:
    • Second- or third-degree atrioventricular block
    • Bifascicular block (defined as left anterior hemiblock in the presence of right bundle branch block)
  • Claudication limiting activity
  • Cerebrovascular events with the past year (including transient ischemic attack)

Other

• No prior allergic reaction to antidiarrheal medications or antiemetics
• No prior severe hypersensitivity reaction to mitoxantrone or other agents formulated with polysorbate 80
• No active infection
• No other concurrent uncontrolled illness
• No diabetes mellitus requiring insulin OR that required pharmacologic intervention for more than 5 years
• No peripheral neuropathy ≥ grade 2
• No other serious medical or psychiatric illness that would preclude study compliance or treatment

Expected Enrollment

A total of 42 patients will be accrued for this study.

Outline

This is a dose-escalation study.

Patients receive bortezomib IV and mitoxantrone IV on days 1, 8, 15, and 22. Treatment repeats every 35 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of patients receive escalating doses of bortezomib and mitoxantrone until the maximum tolerated dose (MTD) is determined using a continuous reassessment method for dose escalation. The MTD is defined as the dose level having a mean posterior dose-limiting toxicity probability closest to 25%.

Patients are followed at 3 weeks.

Siefker-Radtke AO, Poulter V, Mathew P, et al.: Preliminary evidence of efficacy and tolerance for weekly intravenous bortezomib plus mitoxantrone in patients with advanced androgen-independent prostate cancer (AIPCa). [Abstract] J Clin Oncol 23 (Suppl 16): A-4567, 394s, 2005.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Arlene Siefker-Radtke, MD, Protocol chair		Ph: 713-792-2830; 800-392-1611 Email: asiefker@mdanderson.org
Christopher Logothetis, MD, Protocol co-chair		Ph: 713-563-7210; 800-392-1611

Registry Information
Official Title		Phase I Study of Weekly Intravenous PS-341 Plus Mitoxantrone in Patients with Advanced Androgen-Independent Prostate Cancer (Al-PCa)
Trial Start Date		2003-03-24
Registered in ClinicalTrials.gov		NCT00082680
Date Submitted to PDQ		2003-03-24
Information Last Verified		2007-07-03
NCI Grant/Contract Number		CA16672, CA90270

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