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

Phase II Study of Granulocyte-Macrophage Colony Stimulating Factor Plus Mitoxantrone for the Treatment of Hormone Refractory Prostate Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Mitoxantrone; Drug: GM-CSF

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Leukine; Sargramostim; Granulocyte-Macrophage Colony Stimulating Factor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	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)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With > 50% Decrease in Prostate-specific Antigen Levels (PSA Response)	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.	18 months
Overall Survival (OS)	Assessed as the time from the 1st dose of study drug to death.	18 months

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: May 18, 2007
• First Submitted That Met QC Criteria: May 18, 2007
• First Posted (Estimate): May 22, 2007

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antineoplastic Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Mitoxantrone; Sargramostim; Molgramostim
• Other Study ID Numbers: IRB-04738; 96817 (Other Identifier: Stanford University alternate IRB Number); PROS0017 (Other Identifier: OnCore Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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