Prostatic Neoplasms
Conditions
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.
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.
Interventions
DRUGMitoxantrone
Mitoxantrone is an anti-cancer chemotherapy drug that is classified as an antitumor antibiotic.
DRUGGM-CSF
GM-CSF is a biologic response modifier, classified as a colony stimulating factor.
Sponsors
Bayer
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Overall Survival (OS) | 18 months | Assessed as the time from the 1st dose of study drug to death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | GM-CSF Plus Mitoxantrone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 4 / 10 |
Outcome results
Primary
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)
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GM-CSF Plus Mitoxantrone | Progression-free Survival (PFS) | 7.5 weeks |
Secondary
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.
Time frame: 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GM-CSF Plus Mitoxantrone | Number of Participants With > 50% Decrease in Prostate-specific Antigen Levels (PSA Response) | 3 Participants |
Secondary
Overall Survival (OS)
Assessed as the time from the 1st dose of study drug to death.
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GM-CSF Plus Mitoxantrone | Overall Survival (OS) | 7.8 Months |