Phase II GM-CSF Plus Mitoxantrone in Hormone Refractory Prostate Cancer

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00477087
• Collaborator: Bayer (Industry)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 42.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of the combination of mitoxantrone and granulocyte-macrophage colony stimulating factor (GM-CSF) on progression-free survival (PFS) and overall survival (OS), in patients with hormone-refractory prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Mitoxantrone; Drug: GM-CSF	Phase 2

Detailed Description

This trial evaluates if the addition of GM-CSF to standard-of-care therapy after 1st-line docetaxel improves tumor control and survival. Because the 2 drugs have completely different mechanisms of action as well as non-overlapping metabolism, clinically significant drug-drug interactions are not anticipated, and therefore both drugs will be given at standard (approved) doses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Granulocyte-Macrophage Colony Stimulating Factor Plus Mitoxantrone for the Treatment of Hormone Refractory Prostate Cancer
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GM-CSF Plus Mitoxantrone GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days.	Drug: Mitoxantrone; Mitoxantrone is an anti-cancer chemotherapy drug that is classified as an antitumor antibiotic.; Other Names: Novantrone ; Drug: GM-CSF; GM-CSF is a biologic response modifier, classified as a colony stimulating factor.; Other Names: Sargramostim Leukine Granulocyte-Macrophage Colony Stimulating Factor

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [18 months]

   Assessed as the time from the 1st dose of study drug to death or disease progression (increase >25% over baseline PSA on 2 consecutive measurements 2 weeks apart, need for palliative therapy, formation/progression of new bone lesions, or decline of >20% KPS)

Secondary Outcome Measures

1. Number of Participants With > 50% Decrease in Prostate-specific Antigen Levels (PSA Response) [18 months]

   Defined as the first evidence of a total serum PSA decline of > 50% from baseline, maintained for at least 28 days, and confirmed with 2 consecutive measurements taken 2 weeks apart.

2. Overall Survival (OS) [18 months]

   Assessed as the time from the 1st dose of study drug to death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed written informed consent

• Age ≥ 18 years

• Histologically-confirmed adenocarcinoma of the prostate

• Hormone-refractory prostate cancer

• Failed 1st-line docetaxel-containing regimen

• No prior immunotherapy including:

• Vaccines

• GM-CSF

• Minimum prostate-specific antigen (PSA) > 5 mg/dL and rising according to the PSA Consensus Criteria

• Karnofsky Performance Status (KPS) > 60%

• Eastern Cooperative Oncology Group (ECOG) Performance Status < 3

• Life expectancy > 6 months

Exclusion Criteria:

• Concomitant hormonal therapy other than luteinizing hormone-releasing hormone (LHRH) agonist

• Use of herbal products known to decrease PSA levels

• Use of supplements or complementary medicines, except for:

• Conventional multivitamin supplements

• Selenium

• Lycopene

• Soy supplements

• Vitamin E

• Initiation of bisphosphonates within one month prior to enrollment or throughout the study

• Any prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment

• Major surgery or radiation therapy completed < 4 weeks prior to enrollment

• Any concomitant second malignancy other than non-melanoma skin cancer

• Any concomitant serious infection

• Any nonmalignant medical illness

• Absolute neutrophil count (ANC) < 1,500/µL

• Platelet count < 100,000 µL

• Hemoglobin < 8 mg/dL

• Total bilirubin greater than 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN if no demonstrable liver metastases, or greater than 5.0 x ULN in presence of liver metastases

• Ejection fraction < 50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

• Noncompliance with study procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• Bayer

Investigators

• Principal Investigator: Dr. Sandy Srinivas, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandy Srinivas, Associate Professor of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT00477087
• Other Study ID Numbers: IRB-04738; 96817; PROS0017
• First Posted: May 22, 2007
• Last Update Posted: Nov 29, 2017
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Molgramostim; Mitoxantrone; Sargramostim

Study Results

Participant Flow

Arm/Group Title	GM-CSF Plus Mitoxantrone
Arm/Group Description	GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	GM-CSF Plus Mitoxantrone
Arm/Group Description	GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	10 100%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	10 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	10 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 70%
More than one race	0 0%
Unknown or Not Reported	2 20%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	Assessed as the time from the 1st dose of study drug to death or disease progression (increase >25% over baseline PSA on 2 consecutive measurements 2 weeks apart, need for palliative therapy, formation/progression of new bone lesions, or decline of >20% KPS)
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GM-CSF Plus Mitoxantrone
Arm/Group Description	GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days
Measure Participants	10
Median (Full Range) [weeks]	7.5

2. Secondary Outcome

Title	Number of Participants With > 50% Decrease in Prostate-specific Antigen Levels (PSA Response)
Description	Defined as the first evidence of a total serum PSA decline of > 50% from baseline, maintained for at least 28 days, and confirmed with 2 consecutive measurements taken 2 weeks apart.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GM-CSF Plus Mitoxantrone
Arm/Group Description	GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days
Measure Participants	10
Count of Participants [Participants]	3 30%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Assessed as the time from the 1st dose of study drug to death.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GM-CSF Plus Mitoxantrone
Arm/Group Description	GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days
Measure Participants	10
Median (Full Range) [Months]	7.8

Adverse Events

Time Frame	3 years
Arm/Group Title	GM-CSF Plus Mitoxantrone
Arm/Group Description	GM-CSF at 250 micrograms/ m² / day subcutaneously 3 x week for 3 weeks. Participants will also receive mitoxantrone 14 mg/m² on Day 1 of each cycle. Each cycle of therapy consists 21 days
All Cause Mortality
	GM-CSF Plus Mitoxantrone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	GM-CSF Plus Mitoxantrone
	Affected / at Risk (%)	# Events
Total	4/10 (40%)
Blood and lymphatic system disorders
Hematuria	1/10 (10%)	1
Pancytopenic	1/10 (10%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Progressive disease	1/10 (10%)	1
Renal and urinary disorders
Acute renal failure	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	GM-CSF Plus Mitoxantrone
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Cardiac disorders
Chest pain	1/10 (10%)	1
Eye disorders
Dizziness	1/10 (10%)	1
Gastrointestinal disorders
Heartburn	1/10 (10%)	1
Nausea	2/10 (20%)	2
Vomiting	1/10 (10%)	1
General disorders
Fatigue	6/10 (60%)	6
Diarrhea	1/10 (10%)	1
Weight gain	1/10 (10%)	1
Infections and infestations
Dyspnea	4/10 (40%)	4
Nervous system disorders
Night sweats	3/10 (30%)	3
Skin and subcutaneous tissue disorders
Alopecia	1/10 (10%)	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.