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

• ClinicalTrials.gov Identifier: NCT00477087
• Recruitment Status: Terminated
• First Posted: May 22, 2007
• Results First Posted: November 29, 2017
• Last Update Posted: November 29, 2017
• Sponsor: Stanford University
• Collaborator: Bayer
• Information provided by (Responsible Party): Sandy Srinivas, Stanford University

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 (Clinical Trial)
• 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: July 2006
• Actual Primary Completion Date: October 2009
• Actual Study Completion Date: January 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 Name: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 18 months ]
   Assessed as the time from the 1st dose of study drug to death.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: males (prostate cancer)
• Accepts Healthy Volunteers: No

Criteria

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

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Bayer

Investigators

• Principal Investigator: Dr. Sandy Srinivas; Stanford University

More Information

• Responsible Party: Sandy Srinivas, Associate Professor of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT00477087
• Other Study ID Numbers: IRB-04738; 96817 ( Other Identifier: Stanford University alternate IRB Number ); PROS0017 ( Other Identifier: OnCore Number )
• First Posted: May 22, 2007
• Results First Posted: November 29, 2017
• Last Update Posted: November 29, 2017
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• 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; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Molgramostim; Mitoxantrone; Sargramostim; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action