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

Phase 1TerminatedNCT00702923

University of Wisconsin, Madison12 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Prostate Cancer

Bicalutamide and CP-675,206 (Tremelimumab)DRUG

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)

Bicalutamide, CP-675,206 (tremelimumab)DRUG

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)

Bicalutamide, CP-675,206 (Tremelimumab)DRUG

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)

Bicalutamide, CP-675,206 (Tremelimumab)DRUG

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)

Bicalutamide, CP-675,206DRUG

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

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

The Number of Participants Who Developed Cancer Antigen-specific Immune Responses

Time frame: Up to 12 months after treatment with study agent

Secondary Outcomes

The Number of Participants With an Increase in PSA Doubling Time

Time frame: 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.

Time frame: one year