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

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
leflunomide
mitoxantrone hydrochloride
prednisone
Sponsored by
Pfizer
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring stage IV prostate cancer, recurrent prostate cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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 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 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

Sites / Locations

  • Comprehensive Cancer Care Specialists of Boca Raton
  • Florida Cancer Specialists
  • St. Vincents Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
December 10, 1999
Last Updated
September 10, 2012
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00004071
Brief Title
Mitoxantrone and Prednisone With or Without Leflunomide in Treating Patients With Stage IV Prostate Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
August 1999 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
September 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known if mitoxantrone and prednisone are more effective with or without leflunomide for treating prostate cancer. PURPOSE: Randomized phase II/III trial to compare the effectiveness of mitoxantrone and prednisone with or without leflunomide in treating patients who have stage IV prostate cancer that has not responded to hormone therapy.
Detailed Description
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. 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. PROJECTED ACCRUAL: Up to 370 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
stage IV prostate cancer, recurrent prostate cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Allocation
Randomized

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
leflunomide
Intervention Type
Drug
Intervention Name(s)
mitoxantrone hydrochloride
Intervention Type
Drug
Intervention Name(s)
prednisone

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mack H. Mabry, MD
Organizational Affiliation
SUGEN
Official's Role
Study Chair
Facility Information:
Facility Name
Comprehensive Cancer Care Specialists of Boca Raton
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33428
Country
United States
Facility Name
Florida Cancer Specialists
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
St. Vincents Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States

12. IPD Sharing Statement

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

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