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

May 18, 2007
July 3, 2012
July 2006
January 2009   (final data collection date for primary outcome measure)
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 ]
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: two years ]
Complete list of historical versions of study NCT00477087 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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: within the first 3 months ]
  • Time to sustained biochemical response, defined as the time from first administration of drug to first evidence of sustained response [ Time Frame: two years ]
  • Duration of sustained response, defined as time from PSA decrease of >50% from baseline to the first evidence of disease progression [ Time Frame: two years ]
  • Overall survival [ Time Frame: two years ]
Not Provided
Not Provided
 
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 GM-CSF on time to progression in patients with hormone-refractory prostate cancer.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostatic Neoplasms
  • Drug: Mitoxantrone
    14mg/m2 IV
    Other Name: Novantrone
  • Drug: GM-CSF
    250mg 3/week
    Other Names:
    • Sargramostim
    • Leukine
    • Granulocyte-Macrophage Colony Stimulating Factor
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
July 2010
January 2009   (final data collection date for primary outcome measure)

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
Male
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00477087
PROS0017, 96817
Yes
Sandy Srinivas, Stanford University
Stanford University
Bayer
Principal Investigator: Dr. Sandy Srinivas Stanford University
Stanford University
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP