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

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University
ClinicalTrials.gov Identifier:
NCT00477087
First received: May 18, 2007
Last updated: July 3, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to evaluate the effect of the combination of mitoxantrone and GM-CSF on time to progression in patients with hormone-refractory prostate cancer.


Condition Intervention Phase
Prostatic Neoplasms
Drug: Mitoxantrone
Drug: GM-CSF
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Time to Progression - 1st study drug dose to observation of 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: 2 consecutive measurements 2 weeks apart ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 two consecutive measurements taken two weeks apart [ Time Frame: two consecutive measurements taken two weeks apart ] [ Designated as safety issue: No ]
  • Time to sustained biochemical response, defined as the time from first administration of drug to first evidence of sustained response [ Time Frame: as the time from first administration of drug to first evidence of sustained response ] [ Designated as safety issue: No ]
  • Duration of sustained response, defined as time from PSA decrease of >50% from baseline to the first evidence of disease progression [ Time Frame: time from PSA decrease of >50% from baseline to the first evidence of disease progression ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: July 2006
Study Completion Date: July 2010
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Mitoxantrone
    14mg/m2 IV
    Other Name: Novantrone
    Drug: GM-CSF
    250mg 3/week
    Other Names:
    • Sargramostim
    • Leukine
    • Granulocyte-Macrophage Colony Stimulating Factor
Detailed Description:

The purpose of this study is to evaluate the effect of the combination of mitoxantrone and GM-CSF on time to progression in patients with hormone-refractory prostate cancer. To date, there are no curative treatments for prostate cancer that has become hormone-refractory. Treatments appropriate for prostate cancer at this stage include docetaxel, which, in combination with prednisone, has recently been shown to lead to a survival benefit, and mitoxantrone, which, to date, has been shown to lead to a more favorable outcome than steroids alone, but without a survival benefit. GM-CSF is a cytokine that is thought to lead to an enhanced antitumor immune response, presumably through induction of tumor necrosis factor and interleukin-1 expression, as well as growth and proliferation of macrophages and dendritic cells. Both preclinical models and Phase II studies have suggested that GM-CSF as a single agent may have antitumor activity in advanced prostate cancer. To date, the use of GM-CSF for the treatment of prostate cancer has been explored in different contexts, and, more specifically, as a single agent in androgen-independent prostate cancer (AIPC) and hormone-refractory prostate cancer (HRPC), in combination with thalidomide in hormone-naïve prostate cancer and androgen-dependent advanced prostate cancer with ketoconazole in AIPC, and finally with CTLA4 in HRPC. For patients with HRPC who have failed first line chemotherapy, few, non-curative options are available, one of them involving the use of mitoxantrone. On the basis of GM-CSF's mechanism of action, the addition of GM-CSF to a mitoxantrone-containing regimen may lead to enhanced antitumor activity in patients with HRPC.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:- must give signed written informed consent

  • must be of age 18 years or older
  • must have histologically confirmed adenocarcinoma of the prostate
  • must have hormone-refractory prostate cancer
  • must have failed first-line docetaxel-containing regimen
  • must not have had any prior immunotherapy including, but not limited to, vaccines and GM-CSF
  • minimum PSA > 5mg/dL, and rising according to the PSA Consensus Criteria (i.e. progressive disease after androgen deprivation and during first-line docetaxel-based chemotherapy)
  • KPS > 60%
  • Life expectancy of greater than 6 months

Exclusion Criteria:- Concomitant hormonal therapy

  • Noncompliance
  • 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 or nonmalignant medical illness
  • ANC < 1,500/µl, platelet count <100,000/µl, hemoglobin < 8 mg/dl
  • Total bilirubin greater than 1.5 x ULRR
  • ALT or AST greater than 2.5 x ULRR if no demonstrable liver metastases or greater than 5.0 x ULRR in presence of liver metastases
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477087

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

No publications provided

Responsible Party: Sandy Srinivas, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00477087     History of Changes
Other Study ID Numbers: PROS0017, 96817
Study First Received: May 18, 2007
Last Updated: July 3, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Mitoxantrone
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014