RATIONALE: SU5416 may stop the growth of cancer by stopping blood flow to the tumor. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, bicalutamide, leuprolide, or goserelin may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining SU5416, hormone therapy, and radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of SU5416 plus hormone therapy and radiation therapy in treating patients who have prostate cancer.

Condition	Treatment or Intervention	Phase
stage II prostate cancer stage III prostate cancer stage IV prostate cancer adenocarcinoma of the prostate	Procedure: biological response modifier therapy  Procedure: radiation therapy  Procedure: hormone therapy  Procedure: endocrine therapy  Procedure: antiandrogen therapy  Procedure: releasing factor agonist therapy  Procedure: growth factor antagonist therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: protein tyrosine kinase inhibitor therapy  Procedure: enzyme inhibitor therapy  Drug: bicalutamide  Drug: flutamide  Drug: goserelin  Drug: leuprolide  Drug: SU5416	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety of SU5416 in combination with standard androgen ablation and radiotherapy in patients with intermediate or advanced-stage prostate cancer.

PROTOCOL OUTLINE: This is a multicenter, dose-escalation study of SU5416. Patients receive oral bicalutamide once daily or oral flutamide three times daily for at least 1 month followed by leuprolide or goserelin subcutaneously once monthly for four months. Beginning after the fourth administration of leuprolide or goserelin, patients receive radiotherapy 5 days a week for 7-8 weeks. Beginning one month before radiotherapy and continuing until 1 month after radiotherapy, patients receive SU5416 IV over 60 minutes on days 1 and 4. Treatment repeats weekly in the absence of disease progression or unacceptable toxicity. Cohorts of 3-12 patients receive escalating doses of SU5416 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 3 of 12 patients experience dose-limiting toxicity. Patients are followed every 4-6 weeks for 4 months and then every 8-12 weeks for 8 months.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed adenocarcinoma of the prostate with at least 1 of the following: Clinical stage T2b or greater; Gleason score at least 8; Pretreatment PSA greater than 15 ng/mL; Pelvic and/or periaortic node(s) positive on abdominal/pelvic CT scan; Metastatic disease requiring palliation for local symptoms
• No known brain metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No concurrent anticancer chemotherapy
• Endocrine therapy: Prior hormonal therapy of any duration allowed
• Radiotherapy: No prior pelvic radiotherapy
• Surgery: No prior prostatectomy
• Other: No prior non-hormonal systemic therapy for prostate cancer; No other concurrent investigational or commercial agents or therapies for malignancy; No concurrent combination antiretroviral therapy for HIV

--Patient Characteristics--

• Age: Not specified
• Performance status: ECOG 0-2; Karnofsky 60-100%
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 75,000/mm3
• Hepatic: Bilirubin no greater than upper limit of normal (ULN); AST no greater than 2.5 times ULN
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min
• Cardiovascular: No symptomatic congestive heart failure; No cardiac arrhythmia; No uncompensated coronary artery disease on ECG or physical exam; No myocardial infarction or severe unstable angina within the past 6 months; No deep venous or arterial thrombosis within the past 3 months
• Pulmonary: No pulmonary embolism within the past 3 months
• Other: No other concurrent uncontrolled illness; No ongoing or active infection; No diabetes mellitus with severe peripheral vascular disease; No psychiatric illness or social condition that would preclude study; No prior allergic reactions attributed to compounds of similar chemical or biological composition to SU5416 or Cremophor EL vehicle; No prior severe allergic reactions to paclitaxel or docetaxel

Illinois
      LaGrange Memorial Hospital, LaGrange,  Illinois,  60525,  United States
      Radiation Oncology, Chicago,  Illinois,  60612,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States

Study chairs or principal investigators

Walter M. Stadler,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000069024; UCCRC-NCI-4390; NCI-4390
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 9, 2001
ClinicalTrials.gov Identifier:  NCT00026377
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08