CP-675,206 in Combination With Short Term Androgen Deprivation in Patients With Stage D0 Prostate Cancer

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 Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Bicalutamide and CP-675,206 (Tremelimumab); Drug: Bicalutamide, CP-675,206 (tremelimumab); Drug: Bicalutamide, CP-675,206; Drug: Bicalutamide, CP-675,206 (Tremelimumab); Drug: Bicalutamide, CP-675,206 (Tremelimumab)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

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); Other Names: Casodex; Tremelimumab; 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); Other Names: Casodex; Tremelimumab; 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; Other Names: Casodex; Tremelimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Number of Participants Who Developed Cancer Antigen-specific Immune Responses	Up to 12 months after treatment with study agent

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With an Increase in PSA Doubling Time		Up to 18 months after last dose of study agent
Number of Participants With PSA Recurrence.	PSA recurrence is defined as a minimum PSA value of greater or equal to 1.0ng/ml occurring within one year after the last treatment with CP-675,206, with a confirmatory PSA blood teat performed at least 2 weeks later.	one year

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Pfizer

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 18, 2008
• First Submitted That Met QC Criteria: June 19, 2008
• First Posted (Estimate): June 20, 2008

Study Record Updates

• Last Update Posted (Actual): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 13, 2019
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Casodex; Rising PSA; Tremelimumab; Stage D0 Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Hormone Antagonists; Immune Checkpoint Inhibitors; Androgen Antagonists; Tremelimumab; Antibodies, Monoclonal; Bicalutamide; Ipilimumab
• Other Study ID Numbers: CO07808; A534260 (Other Identifier: UW Madison); SMPH/MEDICINE/MEDICINE*H (Other Identifier: UW Madison); H-2008-0086 (Other Identifier: Institutional Review Board); NCI-2011-00713 (Registry Identifier: NCI Trial ID)