Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed any age NCI SWOG-8894 EST-2889, INT-0105

Objectives

I.  Compare, in a randomized, blinded Phase III setting, overall survival and 
progression-free survival of patients with histologically documented Stage D2 
adenocarcinoma of the prostate randomly assigned to treatment with flutamide 
vs. placebo following bilateral orchiectomy.

II.  Compare qualitative and quantitative toxicities of the two treatment 
regimens.

Entry Criteria

Disease Characteristics:

Histologically proven pathologic Stage D2 adenocarcinoma of
the prostate
  Repeat biopsy not needed to confirm clinically obvious
  metastatic disease with prior history of prostate cancer

  Histologic proof required when a different primary site is
  suspected (i.e., a single lung metastasis, hepatic
  metastasis, or other unusual presentations)

Ineligible for any higher priority SWOG protocol

Evidence of progressive metastatic disease required
  (measurable disease not required)

Concurrent registration on SWOG-9039 (quality-of-life protocol)
required and on SWOG-9205 (Prostate-specific antigen study)
optional
  Patients who do not understand English are not required to
  enter SWOG-9039

Prior/Concurrent Therapy:

Biologic therapy:
  No prior or concomitant biological response modifier therapy

Chemotherapy:
  No prior or concomitant chemotherapy

Endocrine therapy:
  No prior or concomitant endocrine therapy

Radiotherapy:
  Prior radiotherapy allowed if metastatic disease is evident

  Concomitant palliative radiotherapy allowed for control of
  severe pain or epidural cord compression during the first 4
  weeks of treatment

  Irradiated lesions may not be used for objective or
  subjective response assessment)

Surgery:
  Prior surgical treatment allowed if metastatic disease is
     evident
  Recovery from effects of any major surgery required

Patient Characteristics:

Age:
  Any age

Performance status:
  SWOG 0-2 (SWOG 3 allowed if secondary to pain)

Hematopoietic:
  WBC at least 3,000

Hepatic:
  Bilirubin normal
  SGOT no more than 2 x ULN
  Elevations due to liver metastases (confirmed by
     immunoperoxidase staining for acid phosphatase and
     prostatic-specific antigen) allowed if cleared with
     Study Coordinator

Renal:
  Creatinine no more than 2 x ULN
  Abnormal renal function secondary to obstruction by
     prostatic cancer will requires urological management
     with stent or nephrostomy tube and must be cleared with
     Study Coordinator

Other:
  No major active infection
  No significant medical illness that would preclude protocol
     treatment or compromise survival
  No second malignancy within 5 years except:
     Adequately treated nonmelanomatous skin cancer
     Any in situ carcinoma
  
Blood/body fluid analyses to determine eligibility and
imaging studies and physical exams for tumor measurement
completed within 14 days prior to registration; screening
exams other than blood/body fluid analyses and imaging
studies of nonmeasurable disease or uninvolved organs
completed within 42 days prior to registration

Expected Enrollment

Approximately 1,250 patients will be entered over about 2.6 years.

Outline

Double-blind, randomized study.  Patients undergo bilateral orchiectomy within 
1 week following registration and begin treatment on Arm I or II within 4 
working days following orchiectomy.

Arm I:  Antiandrogen Therapy.  Flutamide, FLUT, NSC-147834.

Arm II:  Control:  Placebo.

Beer TM, Tangen CM, Bland LB, et al.: The prognostic value of hemoglobin change after initiating androgen-deprivation therapy for newly diagnosed metastatic prostate cancer: A multivariate analysis of Southwest Oncology Group Study 8894. Cancer 107 (3): 489-96, 2006.[PUBMED Abstract]

Glass TR, Tangen CM, Crawford ED, et al.: Metastatic carcinoma of the prostate: identifying prognostic groups using recursive partitioning. J Urol 169 (1): 164-9, 2003.[PUBMED Abstract]

Tangen C, Crawford ED, Faulkner J, et al.: Ten-year survival in patients with metastatic (M+) prostate cancer (CaP): analysis of Southwest Oncology Group (SWOG) 8894. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-749, 2002.

Thompson IM, Tangen C, Basler J, et al.: Impact of previous local treatment for prostate cancer on subsequent metastatic disease. J Urol 168 (3): 1008-12, 2002.[PUBMED Abstract]

Thompson IM, Basler J, Tangen C, et al.: Does a prior radical prostatectomy (RP) alter outcome of hormonal therapy for metastatic (M+) prostate cancer. [Abstract] J Urol 165 (5 suppl): A-689, 168, 2001.

Thompson I, Tangen C, Tolcher A, et al.: Association of African-American ethnic background with survival in men with metastatic prostate cancer. J Natl Cancer Inst 93 (3): 219-25, 2001.[PUBMED Abstract]

Thompson I, Tolcher A, Crawford ED, et al.: African American ethnic background is an independent and negative predictor of survival in metastatic prostate cancer. [Abstract] J Urol 163 (4 suppl): A-242, 56, 2000.

Eisenberger MA, Blumenstein BA, Crawford ED, et al.: Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 339 (15): 1036-42, 1998.[PUBMED Abstract]

Eisenberger M, Crawford ED, McLeod D, et al.: A comparison of bilateral orchiectomy (orch) with or without flutamide in stage D2 prostate cancer (PC) (NCI INT-0105 SWOG/ECOG) . [Abstract] Proceedings of the American Society of Clinical Oncology 16: A-3, 2a, 1997.

Moinpour C, Savage M, Lovato L, et al.: Quality of life endpoints in advanced stage prostate cancer: a randomized double-blind study comparing flutamide to plecebo in orchiectomized stage D2 prostate patients. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A183, 1997.

Eisenberger M, Crawford ED, McLeod D, et al.: The prognostic significance of prostate specific antigen (PSA) in stage D2 prostate cancer (PC) interim evaluation of intergroup study 0105. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-613, 235, 1995.

Montgomery RB, Goldman B, Tangen CM, et al.: Association of body mass index with response and survival in men with metastatic prostate cancer: Southwest Oncology Group trials 8894 and 9916. J Urol 178 (5): 1946-51; discussion 1951, 2007.[PUBMED Abstract]

Blumenstein BA: Overview analysis issues using combined androgen deprivation overview analysis as an example. Urol Oncol 1 (3): 95-100, 1995.

Blumenstein BA: Some statistical considerations for the interpretation of trials of combined androgen therapy. Cancer 72 (12 Suppl): 3834-40, 1993.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Mario Eisenberger, MD, Protocol chair		Ph: 410-614-3511 Email: marioe@jhmi.edu

Eastern Cooperative Oncology Group

David McLeod, MD, JD, FACS, Protocol chair		Ph: 202-782-6408 Email: david.mcleod@na.amedd.army.mil