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

Alternate Title

Mitoxantrone and Prednisone With or Without Leflunomide in Treating Patients With Stage IV Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Completed 18 and over Pharmaceutical / Industry SUGEN-SU101.035 SUGEN-990711, NCT00004071

Objectives

I. Compare the percentage one year survival rate in hormone refractory 
prostate cancer patients treated with leflunomide (SU101), mitoxantrone, and 
prednisone versus mitoxantrone and prednisone alone.

II. Compare the palliative pain response, time to treatment failure, time to 
progression, median survival, investigator global response assessment, 
objective response, time to palliative pain response, duration of palliation, 
and effect on PSA between these two regimens.

III. Assess the safety and tolerability of mitoxantrone in combination with 
SU101 in these patients.

IV. Assess the health related quality of life of these patients on these 
regimens.

Entry Criteria

Disease Characteristics:

Histologically proven hormone refractory stage IV prostate cancer

Hormone refractory disease is defined as:
 Progressive measurable disease OR
 Progressive disease by bone scan OR
 Increase in PSA by 50% over nadir level confirmed twice and measured at least
  two weeks apart 

Prior treatment with primary androgen ablative therapy with castrate levels of
testosterone

Minimum score of 2 on the McGill 6 point pain scale secondary to metastatic
bony pain with an analgesic score of at least 4

No CNS metastases

Prior/Concurrent Therapy:

Biologic therapy:
 At least 4 weeks since prior biologic response modifiers
 At least 4 weeks since prior immunotherapy
 No concurrent immunotherapy

Chemotherapy:
 No prior SU101 or mitoxantrone
 No prior cytotoxic chemotherapy for prostate cancer
 No other concurrent chemotherapy

Endocrine therapy:
 See Disease Characteristics
 At least 4 weeks since prior antiandrogen therapy and recovered
 Concurrent primary androgen ablation therapy (orchidectomy, luteinizing
  hormone releasing hormone (LHRH) agonist (if stable dose), estrogen, or
  cyproterone acetate) allowed 
 No concurrent antiandrogen therapy (except LHRH)
 No concurrent cholestyramine

Radiotherapy:
 At least 4 weeks since prior radiotherapy (8 weeks since strontium 89 and
  samarium 153)
 Prior palliative radiotherapy to metastatic sites allowed
 No prior radiotherapy to greater than 50% of bone marrow
 No concurrent radiotherapy except for palliation of bone pain

Surgery:
 At least 2 weeks since prior major surgery
 No concurrent surgery for prostate cancer

Other:
 At least 4 weeks since prior investigational therapy 
 At least 4 weeks since prior antiangiogenesis therapy
 At least 6 weeks since prior bicalutamide
 No other concurrent investigational therapy
 

Patient Characteristics:

Age:
 18 and over

Performance status:
 Karnofsky 70-100%

Life expectancy:
 Greater than 16 weeks

Hematopoietic:
 Absolute neutrophil count at least 1,500/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin at least 8.0 g/dL (without blood transfusion(s) within 2 weeks
  prior to study)

Hepatic:
 Bilirubin less than 1.5 times upper limit of normal (ULN)
 AST no greater than 2.5 times ULN

Renal:
 Creatinine no greater than 2.0 mg/dL

Cardiovascular:
 No cardiac failure
 No myocardial infarction within the past 6 months
 No uncontrolled hypertension
 LVEF greater than 50%

Other:
 Fertile patients must use effective barrier contraception during and for 3
  months after study
 No known hypersensitivity to polysorbate or polyethylene glycol
 No other malignancies within past 5 years, except basal cell skin cancer
 No other acute or chronic medical, psychiatric, or lab abnormality that would
  prevent compliance
 No uncontrolled peptic ulcer
 No active infection
 No contraindication to mitoxantrone therapy
 No contraindication to prednisone therapy

Expected Enrollment

Up to 370 patients will be accrued for this study.

Outline

This is a randomized, open label, multicenter study. Patients are stratified 
by performance status (70-80% vs 90-100%), baseline present pain intensity 
score (2.0 vs greater than 2.0), and hemoglobin level (less than 12.0 g/dL vs 
at least 12.0 g/dL).

Patients enter one of two treatment arms:

Arm I: Patients are premedicated with an IV 5-HT3 reuptake inhibitor (i.e., 
odansetron) then receive mitoxantrone IV on day 1.  Twice daily oral 
prednisone therapy begins on day 1 and continues throughout study treatment.  
Treatment repeats every 21 days for 4 courses.

Arm II: Patients are premedicated with an IV 5-HT3 reuptake inhibitor as in 
arm I.  Patients receive mitoxantrone and prednisone therapy as in arm I.  
Additionally, beginning on day 1 patients receive leflunomide (SU101) IV over 
4-5 hours weekly for 12 weeks.  The SU101 infusions shall precede mitoxantrone 
infusions.  Patients receive a maximum of one year therapy with SU101; 
mitoxantrone therapy may be administered up to a maximum dose of 140/m2.

Quality of life is assessed at baseline, day 8, day 21, and then every 3 weeks 
thereafter until study completion.

Patients are followed at least every 2 months.

Trial Contact Information

Trial Lead Organizations

SUGEN, Incorporated - South San Francisco

Mack H. Mabry, MD, Protocol chair		Ph: 650-837-3300

Registry Information
Official Title		A Randomized, Open-Label Phase II/III Study of SU101 Plus Mitoxantrone/Prednisone Compared to Mitoxantrone/Prednisone Alone in Patients with Hormone-Refractory Prostate Cancer
Trial Start Date		1999-08-09
Registered in ClinicalTrials.gov		NCT00004071
Date Submitted to PDQ		1999-08-24
Information Last Verified		2007-06-01