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

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00702923
• Collaborator: Pfizer (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 56
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Bicalutamide and CP-675,206 (Tremelimumab); Drug: Bicalutamide, CP-675,206 (tremelimumab); Drug: Bicalutamide, CP-675,206 (Tremelimumab); Drug: Bicalutamide, CP-675,206 (Tremelimumab); Drug: Bicalutamide, CP-675,206	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jul 1, 2008
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

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 (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); Other Names: Casodex Tremelimumab ; 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); 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

Outcome Measures

Primary Outcome Measures

1. The Number of Participants Who Developed Cancer Antigen-specific Immune Responses [Up to 12 months after treatment with study agent]

Secondary Outcome Measures

1. The Number of Participants With an Increase in PSA Doubling Time [Up to 18 months after last dose of study agent]

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Wisconsin Carbone Cancer Center

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00702923
• Other Study ID Numbers: CO07808; CO07808; H-2008-0086; NCI-2011-00713; A534260; SMPH/MEDICINE/MEDICINE*H
• First Posted: Jun 20, 2008
• Last Update Posted: Nov 21, 2019
• Last Verified: Apr 1, 2014

• Keywords provided by University of Wisconsin, Madison: Stage D0 Prostate Cancer; Rising PSA; Casodex; Tremelimumab
• Additional relevant MeSH terms: Prostatic Neoplasms; Tremelimumab; Bicalutamide; Ipilimumab; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	CP-675,206 in Combination With Short Term Androgen Deprivation
Arm/Group Description	Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3
Period Title: Overall Study
STARTED	12
COMPLETED	11
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	CP-675,206 in Combination With Short Term Androgen Deprivation
Arm/Group Description	Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 58.3%
>=65 years	5 41.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.7 (5.2)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	12 100%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CP-675,206 3mg/kg	CP-675,206 6mg/kg
Arm/Group Description	Dose level -1: Bicalutamide 150mg orally once a day on days 1-28 and CP-675,206 3mg/kg intravenously over 1 hour on day 29. The treatment is repeated at month 3 (beginning day 85).	Dose level 1: Bicalutamide 150mg orally once a day on days 1-28 and CP-675,206 6mg/kg intravenously over 1 hour on day 29. The treatment is repeated at month 3 (beginning day 85).
Measure Participants	6	5
one or more prostate-associated antigens	6 50%	5 NaN
antibodies specific for PSA	2 16.7%	1 NaN

2. Secondary Outcome

Title	The Number of Participants With an Increase in PSA Doubling Time
Time Frame	Up to 18 months after last dose of study agent

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CP-675,206 3mg/kg	CP-675,206 6mg/kg
Arm/Group Description	Dose level -1: Bicalutamide 150mg orally once a day on days 1-28 and CP-675,206 3mg/kg intravenously over 1 hour on day 29. The treatment is repeated at month 3 (beginning day 85).	Dose level 1: Bicalutamide 150mg orally once a day on days 1-28 and CP-675,206 6mg/kg intravenously over 1 hour on day 29. The treatment is repeated at month 3 (beginning day 85).
Measure Participants	6	5
immediate post-treatment period (6-12 months)	0 0%	0 NaN
12-18 months after treatment	2 16.7%	1 NaN

3. Secondary Outcome

Title	Number of Participants With PSA Recurrence.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CP-675,206 3mg/kg	CP-675,206 6mg/kg
Arm/Group Description	Dose level -1: Bicalutamide 150mg orally once a day on days 1-28 and CP-675,206 3mg/kg intravenously over 1 hour on day 29. The treatment is repeated at month 3 (beginning day 85).	Dose level 1: Bicalutamide 150mg orally once a day on days 1-28 and CP-675,206 6mg/kg intravenously over 1 hour on day 29. The treatment is repeated at month 3 (beginning day 85).
Measure Participants	6	5
Number [participants]	6 50%	5 NaN

Adverse Events

Arm/Group Title	CP-675,206 in Combination With Short Term Androgen Deprivation
Arm/Group Description	Bicalutamide 150mg orally days 1-28 followed by CP-675,206 IV on day 29. Cycle is repeated once at month 3
All Cause Mortality
	CP-675,206 in Combination With Short Term Androgen Deprivation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CP-675,206 in Combination With Short Term Androgen Deprivation
	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)
Gastrointestinal disorders
Colitis	1/12 (8.3%)	1
Immune system disorders
Autoimmune Reaction	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	CP-675,206 in Combination With Short Term Androgen Deprivation
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Edema: limb	2/12 (16.7%)	2
Cardiac disorders
Hypertension	1/12 (8.3%)	1
Hypotension	1/12 (8.3%)	1
Endocrine disorders
Hot flashes/flushes	4/12 (33.3%)	6
Eye disorders
Dry eye syndrome	1/12 (8.3%)	1
Ocular/Visual--Other	1/12 (8.3%)	1
Gastrointestinal disorders
Constipation	2/12 (16.7%)	2
Anorexia	2/12 (16.7%)	2
Constipation	3/12 (25%)	3
Diarrhea	3/12 (25%)	9
Distension/bloating, abdominal	2/12 (16.7%)	3
Gastrointestinal--Other	1/12 (8.3%)	1
Incontinence, anal	1/12 (8.3%)	1
Mucositis/sttomatitis (clinical exam)--Oral Cavity	2/12 (16.7%)	3
Mucositis/stomatitis (functional/symptomatic) --Anus	1/12 (8.3%)	1
Mucositis/stomatits (functional/symptomatic)--Oral Cavity	1/12 (8.3%)	1
Nausea	3/12 (25%)	5
Pain--Abdomen NOS	4/12 (33.3%)	6
General disorders
Fatigue	7/12 (58.3%)	11
Fever	1/12 (8.3%)	1
Rigors/chills	2/12 (16.7%)	2
Weight Loss	1/12 (8.3%)	1
flu-like syndrome	1/12 (8.3%)	1
Immune system disorders
Allergic Rhinitis	2/12 (16.7%)	2
Autoimmune Reaction	1/12 (8.3%)	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils--Sinus	1/12 (8.3%)	1
Infection with normal ANC or Grade 1 or 2 neutrophils--Skin	1/12 (8.3%)	1
Investigations
Amylase	1/12 (8.3%)	2
Musculoskeletal and connective tissue disorders
Fracture	1/12 (8.3%)	1
Muscle weakness, generalized or specific area--Extremity-lower	1/12 (8.3%)	1
Pain - Joint	1/12 (8.3%)	1
Pain - neck	1/12 (8.3%)	1
Nervous system disorders
Dizziness	1/12 (8.3%)	1
Mood alteration--Agitation	1/12 (8.3%)	1
Mood alteration--Anxiety	1/12 (8.3%)	1
Mood alteration--Depression	2/12 (16.7%)	4
Neurology--Other	1/12 (8.3%)	1
Pain - Head/headache	1/12 (8.3%)	1
Renal and urinary disorders
Hemorrhage, GU--Bladder	1/12 (8.3%)	1
Hemorrhage, Gu--Urinary NOS	2/12 (16.7%)	2
Hemorrhage/bleeding--Other	1/12 (8.3%)	1
Renal/Genitourinary--Other	1/12 (8.3%)	2
Urinary frequency/urgency	2/12 (16.7%)	2
Urinary retention	2/12 (16.7%)	3
Reproductive system and breast disorders
Gynecomastia	4/12 (33.3%)	4
Pain - Breast	3/12 (25%)	3
Respiratory, thoracic and mediastinal disorders
Cough	1/12 (8.3%)	1
Dyspnea	2/12 (16.7%)	2
Voice changes/dysarthiria	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other	3/12 (25%)	4
Dry Skin	1/12 (8.3%)	1
Hair Loss/Alopecia	1/12 (8.3%)	1
Pruritus/itching	4/12 (33.3%)	5
Rash/desquamation	3/12 (25%)	3
Acne/acneiform	4/12 (33.3%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.