Official Title: “Phase I Dose Escalation Trial of CP-675,206 (Tremelimumab, Anti-CTLA-4 Monoclonal Antibody) in Combination With Short Term Androgen Deprivation in Patients With Stage D0 Prostate Cancer”

The current protocol will evaluate the safety of combining treatment with bicalutamide(Casodex) and CP-675,206 (anti-CTLA-4 monoclonal antibody) in patients with PSA-recurrent non-metastatic (stage D0) prostate cancer. This is a dose escalation study with safety the primary endpoint. Secondary endpoints will be to determine whether prostate associated immune responses are seen, and whether treatment is associated with an increase in PSA doubling time and PSA recurrence at one year, as markers of clinical activity. Cohorts of six patients will be treated in each dose level. The investigators hypothesize that short-term androgen deprivation therapy will elicit prostate cancer-associated T-cell mediated tissue destruction that can be augmented with a monoclonal antibody blocking CTLA-4, and that this will have therapeutic benefit in patients with recurrent prostate cancer.

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

This is an open label, single-center Phase I study. All subjects will receive bicalutamide 150mg orally days 1-28. Subjects will receive CP-675,206 IV over one hour on day 29. Doses will range from 6 mg/kg to 15 mg/kg. This cycle will be repeated once at month 3. Once the maximum tolerated dose has been determined, up to 6 additional subjects will be enrolled.

Intervention(s) in this Clinical Trial

• Drug: Bicalutamide and CP-675,206 (Tremelimumab)
  • Dose level -1 : Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 3 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)
• Drug: Bicalutamide, CP-675,206 (tremelimumab)
  • Dose level 1: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 6 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)
• Drug: Bicalutamide, CP-675,206 (Tremelimumab)
  • Dose level 2: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 10 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)
• Drug: Bicalutamide, CP-675,206 (Tremelimumab)
  • Dose level 3: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 15 mg/kg I.V. over 1 hour, day 29 Cycle repeated once at month 3 (beginning day 85 +/- 7)
• Drug: Bicalutamide, CP-675,206
  • Final Dose Level: Bicalutamide 150 mg p.o. q.d. day 1-28, day 85-112 At month 9, if evidence of PSA progression: Bicalutamide 150 mg p.o. q.d. day 1-28 CP-675,206 (MTD dose) I.V. over 1 hour, day 29

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3

Primary Measures

• The purpose of this research is to determine the safety of CP-675,206 when delivered in combination with short-term androgen deprivation therapy in patients with PSA-recurrent non-metastatic prostate cancer.
  • Time Frame: Up to 12 months after treatment with study agent
    Safety Issue?: Yes

Secondary Measures

• To determine whether prostate associated immune responses are elicited and whether treatment is associated with an increase in PSA doubling time and PSA recurrence at one year.
  • Time Frame: Up to 12 months after last dose of study agent
    Safety Issue?: No

Inclusion Criteria:

• At least 18 years of age & histologic diagnosis of adenocarcinoma of the prostate
• Completed surgery or radiation at least 8 weeks prior to entry with removal of all visible disease
• Clinical Stage D0 prostate cancer with rising PSA and PSA >2ng/ml.
• ECOG performance of <2
• Normal hematologic, renal and liver function

Exclusion Criteria:

• Cannot have evidence of immunosuppression or have been treated with immunosuppressive therapy.
• No prior treatment with an LHRH agonist or nonsteroidal antiandrogen such as casodex or flutamide
• No evidence for metastatic disease per bone scan or CT scan of the abdomen and pelvis
• No prior treatment with anti-CTLA 4 monoclonal antibody
• No history of known autoimmune disorder or HIV, hepatitis B or hepatitis C
• No known brain metastases
• No history of inflammatory bowel conditions including diverticulitis, ulcerative colitis, etc.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Wisconsin, Madison

Overall Clinical Trial Officials and Contacts

Douglas McNeel, MD, PhD Principal Investigator University of Wisconsin, Madison  

Overall Contact: Cancer Connect Clinical Trials Office 1-800-622-8922 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00702923

Study ID Number: H2008-0086

ClinicalTrials.gov Identifier: NCT00702923

Health Authority: United States: Food and Drug Administration