Prostate Cancer
Conditions
Keywords
Stage D0 Prostate Cancer, Rising PSA, Casodex, Tremelimumab
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.
Interventions
DRUGBicalutamide 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)
DRUGBicalutamide, 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)
DRUGBicalutamide, 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)
DRUGBicalutamide, 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
Sponsors
Pfizer
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Number of Participants Who Developed Cancer Antigen-specific Immune Responses | Up to 12 months after treatment with study agent |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | one year | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CP-675,206 in Combination With Short Term Androgen Deprivation Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3 | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | CP-675,206 in Combination With Short Term Androgen Deprivation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 64.7 years STANDARD_DEVIATION 5.2 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 1 / 12 |
Outcome results
Primary
The Number of Participants Who Developed Cancer Antigen-specific Immune Responses
Time frame: Up to 12 months after treatment with study agent
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-675,206 3mg/kg | The Number of Participants Who Developed Cancer Antigen-specific Immune Responses | one or more prostate-associated antigens | 6 participants |
| CP-675,206 3mg/kg | The Number of Participants Who Developed Cancer Antigen-specific Immune Responses | antibodies specific for PSA | 2 participants |
| CP-675,206 6mg/kg | The Number of Participants Who Developed Cancer Antigen-specific Immune Responses | one or more prostate-associated antigens | 5 participants |
| CP-675,206 6mg/kg | The Number of Participants Who Developed Cancer Antigen-specific Immune Responses | antibodies specific for PSA | 1 participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CP-675,206 3mg/kg | Number of Participants With PSA Recurrence. | 6 participants |
| CP-675,206 6mg/kg | Number of Participants With PSA Recurrence. | 5 participants |
Secondary
The Number of Participants With an Increase in PSA Doubling Time
Time frame: Up to 18 months after last dose of study agent
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CP-675,206 3mg/kg | The Number of Participants With an Increase in PSA Doubling Time | 12-18 months after treatment | 2 participants |
| CP-675,206 3mg/kg | The Number of Participants With an Increase in PSA Doubling Time | immediate post-treatment period (6-12 months) | 0 participants |
| CP-675,206 6mg/kg | The Number of Participants With an Increase in PSA Doubling Time | immediate post-treatment period (6-12 months) | 0 participants |
| CP-675,206 6mg/kg | The Number of Participants With an Increase in PSA Doubling Time | 12-18 months after treatment | 1 participants |