GM-CSF in Treating Patients With Relapsed Prostate Cancer

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00908141
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 49
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Colony stimulating factors, such as GM CSF, may increase the number of immune cells found in bone marrow or peripheral blood. It is not yet known which GM-CSF regimen is more effective in treating patients with prostate cancer.

PURPOSE: This randomized phase II trial is studying how well GM-CSF works in treating patients with relapsed prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: sargramostim	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To determine the ability of sargramostim (GM-CSF) to increase the number and activation of dendritic cells (DC) in patients with biochemically relapsed prostate cancer.

Secondary

• To determine the effect of administration schedule and hormonal state on sargramostim-induced DC number and activation in these patients.

• To correlate the effects of sargramostim on DC number and activation with effects on prostate-specific antigen (PSA) modulation.

• To determine whether sargramostim administration generates antiprostate cancer immune responses in these patients.

OUTLINE: Patients are stratified according to hormonal status (androgen-dependent vs androgen-independent). Patients are then randomized to 1 of 2 treatment arms.

• Arm I: Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-14. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive GM-CSF SC three times weekly for 4 weeks. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for dendritic cell (DC) number by flow cytometry, DC activation by quantitative real-time polymerase chain reaction (QRT-PCR), and immunity by serological analysis of recombinant cDNA expression libraries (SEREX).

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immunologic Effects of GM-CSF (Sargramostim, Leukine®) in Patients With Biochemically-relapsed Prostate Cancer
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I: sargramostim (days1-14) Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-14. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Biological: sargramostim; Given subcutaneously on varying schedule
Experimental: Arm II: sargramostim (3xweek) Patients receive GM-CSF SC three times weekly for 4 weeks. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Biological: sargramostim; Given subcutaneously on varying schedule

Outcome Measures

Primary Outcome Measures

1. Prostate Specific Antigen (PSA) Response [post treatment at 9 weeks]

   The number of patients with PSA modulation defined as PSA decline of at least 50%

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• Non-metastatic, recurrent systemic disease as manifested by a rising PSA, defined as ≥ 2 consecutive rises in PSA to be documented over a reference value (measure

• The first rising PSA (measure 2) should be at taken ≥ 14 days after the reference value

• A third confirmatory PSA measure is required (second beyond the reference level) to be greater than the second, and it must be obtained ≥ 14 days after the second measure

• If this is not the case, a fourth PSA is required to be taken and be greater than the second measure

• No local-only relapse

• Must have undergone prior definitive therapy for prostate cancer consisting of external beam radiotherapy, brachytherapy (with or without external beam radiotherapy), or radical prostatectomy (with or without adjuvant androgen ablation)

• Patients who have not undergone definitive therapy as above or who have undergone hormonal therapy alone are not eligible

• No evidence of metastases on bone or CT scan

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• Leukocytes ≥ 3,000/μl

• Absolute neutrophil count ≥ 1,500/μl

• Platelets ≥ 100,000/μl

• Total bilirubin normal

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

• Creatinine ≤ 1.5 times ULN

• No active thrombophlebitis or disseminated intravascular coagulopathy

• No history of pulmonary embolus

• No history of immunodeficiency or autoimmune diseases

• No uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy for any reason

• No concurrent anticoagulation therapy (i.e., therapeutic coumadin)

• Prophylactic anticoagulation (e.g., aspirin) allowed

• No concurrent systemic corticosteroids or other immunosuppressives

• Inhaled or topical steroids allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Robert Dreicer, MD, FACP, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00908141
• Other Study ID Numbers: CASE6805; P30CA043703; CASE6805; 8201
• First Posted: May 25, 2009
• Last Update Posted: Aug 23, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Case Comprehensive Cancer Center: adenocarcinoma of the prostate; recurrent prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Sargramostim

Study Results

Participant Flow

Recruitment Details	Patients recruited from local medical clinic from June 2006 to August 2010.

Arm/Group Title	Group A: Sargramostim (Days 1-14)	Group B:Sargramostim (3 x Week)
Arm/Group Description	GROUP A: Sargramostim 250ug/m2/day subcutaneously (s.c.) on days 1-14 of a 28-day cycle	GROUP B: Sargramostim 250ug subcutaneously (s.c.) three times a week continuously
Period Title: Overall Study
STARTED	8	9
COMPLETED	8	8
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Group A: Sargramostim (Days 1-14)	Group B: Sargramostim (3 x Week)	Total
Arm/Group Description	GROUP A: Sargramostim 250ug/m2/day subcutaneously (s.c.) on days 1-14 of a 28-day cycle	GROUP B: Sargramostim 250ug subcutaneously (s.c.) three times a week continuously	Total of all reporting groups
Overall Participants	8	9	17
Age, Customized (participants) [Number]
40-49 years	1 12.5%	0 0%	1 5.9%
50-59 years	2 25%	2 22.2%	4 23.5%
60-69 years	2 25%	4 44.4%	6 35.3%
70-79 years	3 37.5%	3 33.3%	6 35.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	9 100%	17 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	9 100%	17 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	8 88.9%	16 94.1%
More than one race	0 0%	1 11.1%	1 5.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	9 100%	17 100%

Outcome Measures

1. Primary Outcome

Title	Prostate Specific Antigen (PSA) Response
Description	The number of patients with PSA modulation defined as PSA decline of at least 50%
Time Frame	post treatment at 9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A: Sargramostim (Days 1-14)	Group B: Sargramostim (3 x Week)
Arm/Group Description	GROUP A: Sargramostim 250ug/m2/day subcutaneously (s.c.) on days 1-14 of a 28-day cycle	GROUP B: Sargramostim 250ug subcutaneously (s.c.) three times a week continuously
Measure Participants	8	8
Number [participants]	2 25%	0 0%

Adverse Events

Time Frame	All patients will be evaluable for toxicity from the time of their first treatment with sargramostim through follow up over an approximate three year period.
Arm/Group Title	Group A: Sargramostim (Days 1-14)		Group B: Sargramostim (3 x Week)
Arm/Group Description	GROUP A: Sargramostim 250ug/m2/day subcutaneously (s.c.) on days 1-14 of a 28-day cycle		GROUP B: Sargramostim 250ug subcutaneously (s.c.) three times a week continuously
All Cause Mortality
	Group A: Sargramostim (Days 1-14)		Group B: Sargramostim (3 x Week)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A: Sargramostim (Days 1-14)		Group B: Sargramostim (3 x Week)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		2/9 (22.2%)
Renal and urinary disorders
Ureteral obstruction	0/8 (0%)		1/9 (11.1%)
Vascular disorders
Thrombosis	0/8 (0%)		1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Group A: Sargramostim (Days 1-14)		Group B: Sargramostim (3 x Week)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		9/9 (100%)
Blood and lymphatic system disorders
Infection with normal ANC, intermittent	0/8 (0%)		1/9 (11.1%)
Infection with unknown ANC(Absolute neutrophil count)	0/8 (0%)		1/9 (11.1%)
Lymphopenia	0/8 (0%)		1/9 (11.1%)
Thrombocytopenia	0/8 (0%)		1/9 (11.1%)
Cardiac disorders
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)	1/8 (12.5%)		0/9 (0%)
Gastrointestinal disorders
Abdominal pain or cramping	1/8 (12.5%)		1/9 (11.1%)
Constipation	0/8 (0%)		1/9 (11.1%)
Diarrhea patients without colostomy	1/8 (12.5%)		1/9 (11.1%)
Dyspepsia/heartburn	1/8 (12.5%)		0/9 (0%)
GI symptoms of nausea, emesis, and diarrhea	1/8 (12.5%)		0/9 (0%)
Intermittent rectal hemorrhage	0/8 (0%)		1/9 (11.1%)
General disorders
Fatigue	3/8 (37.5%)		2/9 (22.2%)
Flu-like Symptoms	0/8 (0%)		1/9 (11.1%)
Pain (Back and Left arm)	1/8 (12.5%)		0/9 (0%)
Investigations
Creatinine, elevated	0/8 (0%)		2/9 (22.2%)
Elevated SGOT (AST) (serum glutamic oxaloacetic transaminase)	0/8 (0%)		1/9 (11.1%)
Elevated SGPT (ALT) (serum glutamic pyruvic transaminase)	0/8 (0%)		1/9 (11.1%)
Hemoglobin	1/8 (12.5%)		2/9 (22.2%)
Weight loss	1/8 (12.5%)		0/9 (0%)
Metabolism and nutrition disorders
Hyperglycemia	0/8 (0%)		3/9 (33.3%)
Hyperkalemia	1/8 (12.5%)		1/9 (11.1%)
Hypernatremia	0/8 (0%)		1/9 (11.1%)
Hyponatremia	0/8 (0%)		1/9 (11.1%)
Hypophosphatemia	0/8 (0%)		1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia (joint pain)	0/8 (0%)		1/9 (11.1%)
Leg cramps	1/8 (12.5%)		2/9 (22.2%)
Mid-low back pain	1/8 (12.5%)		0/9 (0%)
Myalgias	1/8 (12.5%)		0/9 (0%)
Neck pain	1/8 (12.5%)		0/9 (0%)
Pain Left buttock	1/8 (12.5%)		0/9 (0%)
Pain, Right knee	0/8 (0%)		1/9 (11.1%)
Pain, sciatic (right)	1/8 (12.5%)		0/9 (0%)
Nervous system disorders
Headache	0/8 (0%)		1/9 (11.1%)
Neuropathy-sensory	0/8 (0%)		1/9 (11.1%)
Psychiatric disorders
Anxiety	1/8 (12.5%)		0/9 (0%)
Insomnia	1/8 (12.5%)		0/9 (0%)
Renal and urinary disorders
Hemoglobinuria	1/8 (12.5%)		0/9 (0%)
Urinary frequency/urgency	2/8 (25%)		1/9 (11.1%)
Urinary incontinence	1/8 (12.5%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)		0/9 (0%)
Sore throat	1/8 (12.5%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/8 (12.5%)		0/9 (0%)
Flushing	1/8 (12.5%)		0/9 (0%)
Injection site reaction	7/8 (87.5%)		8/9 (88.9%)
Rash/desquamation	1/8 (12.5%)		1/9 (11.1%)
Sweating (diaphoresis)	1/8 (12.5%)		0/9 (0%)
Vascular disorders
Hot flashes	0/8 (0%)		2/9 (22.2%)
Hypertension	0/8 (0%)		1/9 (11.1%)

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.