To determine the time to progression produced by the combination of Novantrone (mitoxantrone) and Erbitux (cetuximab) versus Novantrone alone in metastatic AIPC patients previously treated with docetaxel-based chemotherapy. TTP is defined as time from the start of treatment date to the date the patient is first recorded as having disease progression, even in patients who discontinue study treatment early due to toxicity.
This is a nonblinded, randomized phase II study to determine the activity of Novantrone (mitoxantrone) with or without Erbitux (cetuximab) in patients with androgen independent prostate cancer (AIPC) who have been treated previously with docetaxel chemotherapy. The Novantrone (mitoxantrone)-only treatment arm will serve as a concurrent control arm to aid in the determination of the benefit of the Novantrone (mitoxantrone)-Erbitux (cetuximab) combination in this setting. Patients will be randomly assigned 2:1 to 1 of 2 treatment arms; 93 patients in Arm 1 and 47 patients in Arm 2. A balanced randomization procedure will be performed utilizing a code list that will be developed prior to the study opening. Because the patients will be stratified by performance status (ECOG 0 and 1 vs. ECOG 2), the list will be developed to ensure a balance between the 2 treatment arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
115
Erbitux (cetuximab) IV over 2 hours (loading dose) on Day 1 (Cycle 1 only), followed by Erbitux (cetuximab) IV over 1 hour weekly thereafter
Novantrone (mitoxantrone) IV Day 1 + Prednisone QD for ten (10) 21-day cycles Standard androgen deprivation therapy (ADT) will be continued in all patients who enter study on LHRH agonists
Median Time to Progression (TTP)
TTP will be measured from the start of treatment date to the date the patient is first recorded as having disease progression (even in patients who discontinue study treatment early due to toxicity or death due to disease progression.
Time frame: 24 months
2-year Radiographically Evident Progression-free Survival (REPFS).
Radiographic progression: 1\) For bone scan, 2 unequivocal new lesions confirmed by a subsequent bone scan with at least 1 more new lesion; 2) Skeletal related event (eg, fracture, need for radiation to bone for pain, spinal cord compression, need for surgery to bone to prevent or treat a pathologic fracture).
Time frame: 24 months.
Objective Response Rate (ORR)
ORR = CR + PR Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
Time frame: 24 months
Median Time to Prostate-specific Antigen (PSA) Progression
Defined as the time from initiation of therapy until the first 25% increase from baseline in non-responders or 50% increase from nadir in responders as defined above. A minimum increase in the PSA of 5 ng/mL will be required for progression.
Time frame: 24 months
Prostate-specific Antigen (PSA) Response Rate
Defined as the fraction of patients with a ≥50% reduction in serum PSA confirmed by a second serum PSA at least 3 weeks later
Time frame: 24 months
Prostate-specific Antigen (PSA) Doubling Time
PSA doubling time = \[log (2)× t\] ÷ \[log (final PSA) - log (initial PSA)\]
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Phoenix, Arizona, United States
Northern AZ Hematology & Oncology Assoc
Sedona, Arizona, United States
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Denver, Colorado, United States
Melbourne Internal Medicine Associates
Melbourne, Florida, United States
Florida Cancer Institute - New Hope
New Port Richey, Florida, United States
Ocala Oncology Center
Ocala, Florida, United States
Cancer Centers of Florida, P.A.
Ocoee, Florida, United States
Cancer Care & Hematology Specialists of Chicagoland
Niles, Illinois, United States
Central Indiana Cancer Centers
Indianapolis, Indiana, United States
Hope Center
Terre Haute, Indiana, United States
...and 45 more locations
Time frame: 24 months
Median Progression-free Survival (PFS)
PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.
Time frame: 24 months
Median Overall Survival (OS)
OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Time frame: 30 months