Clinical trial NCT00702923: CP-675,206 in Combination With Short Term Androgen Deprivation in Patients With Stage D0 Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: Stage D0 Prostate Cancer
Rising PSA
Casodex
Tremelimumab
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2008-06-20
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Participants Who Developed Cancer Antigen-specific Immune Responses
timeFrame: Up to 12 months after treatment with study agent
Secondary outcomes:
measure: The Number of Participants With an Increase in PSA Doubling Time
timeFrame: Up to 18 months after last dose of study agent
measure: Number of Participants With PSA Recurrence.
timeFrame: one year
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Douglas McNeel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: