Mitoxantrone ± Cetuximab 2nd Line Androgen Independent Prostate Cancer (AIPC)
- Conditions
- Androgen-independent Prostate Cancer
- Interventions
- Registration Number
- NCT00661492
- Lead Sponsor
- US Oncology Research
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 115
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Histologically confirmed adenocarcinoma of the prostate. Note: Patients may have either measurable or non-measurable disease.
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Radiographic evidence of regional or distant metastases
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Current evidence of progression (by PSA and/or imaging studies) despite standard hormonal therapy.
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Progression by PSA will be defined as: A rising PSA defined as: at least 2 rises in PSA over a reference value (PSA #1). The first rising PSA (PSA #2) must be taken at least 1 week after PSA #1. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2. Progression for nonmeasurable disease will be defined as 2 or more new bone lesions; for measurable disease, progression will be defined by standard RECIST criteria.
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For patients who have been on antiandrogen therapy (ie, bicalutamide, flutamide, etc.), patients must have discontinued anti-androgen therapy for at least 6 weeks (4 weeks for flutamide) without evidence of an antiandrogen withdrawal response. A washout period will not be required for patients who did not respond to an antiandrogen prescribed as second line hormonal therapy. For patients whose progression is documented by PSA, the last required PSA must be after the required anti-androgen washout period (4-6 weeks as appropriate).
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One prior docetaxel-containing regimen. Patients must have received at least 2 doses in an every 3-week schedule or 6 doses on a weekly schedule of docetaxel. Patients may have discontinued therapy due to progression, intolerance, completion of planned therapy, or other reasons. Chemotherapy treatment with any second-line regimen will not be permitted. Patients who have been previously treated with a first-line docetaxel-based doublet regimen will be eligible for this study, (eg, patients treated on a prior first-line trial containing a docetaxel/carboplatin or other docetaxel-based doublet).
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Serum testosterone levels (See protocol for specific details) (unless surgically castrate). Patients must continue androgen deprivation with an LHRH agonist if they have not undergone orchiectomy
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ECOG performance status
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Laboratory criteria for entry:
- absolute neutrophil count
- platelets
- bilirubin
- AST or ALT
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Life expectancy greater than 3 months
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Age greater than or equal to 18 years
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Agree to use contraceptives while on study if sexually active, and for 2 months after the last dose of study drug.
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Has signed a Patient Informed Consent Form
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Has signed a Patient Authorization Form
- More than 1 prior chemotherapy regimen for metastatic disease
- Prior history of uncontrolled congestive heart failure or left ventricular ejection fraction (LVEF) that is less than the institution's lower limit of normal on MUGA or echocardiogram
- A second active malignancy (diagnosed within 5 years) except adequately treated non-melanoma skin cancer or other non-invasive or in-situ neoplasm
- Significant active concurrent medical illness or infection
- Treatment with chemotherapy for AIPC within the past 21 days
- Prior treatment with Novantrone (mitoxantrone)
- Prior therapy which specifically and directly targets the EGFR pathway
- Prior severe infusion reaction to a monoclonal antibody
- Recent myocardial infarction (within prior 6 months)
- Prior treatment with radionuclides, with the exception of prior treatment with samarium, which will be allowed provided at least 8 weeks have passed since administration.
- Is receiving concurrent immunotherapy, hormonal therapy, radiation therapy, or any other non-protocol therapy (excluding LHRH antagonist)
- Is receiving concurrent investigational therapy or has received such therapy within the past 30 days
- Has evidence of CNS involvement
- Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection.
- Is unable to comply with requirements of study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 cetuximab Erbitux (cetuximab) and Novantrone (mitoxantrone) Arm 1 Mitoxantrone Erbitux (cetuximab) and Novantrone (mitoxantrone) Arm 2 Mitoxantrone Novantrone (mitoxantrone)
- Primary Outcome Measures
Name Time Method Median Time to Progression (TTP) 24 months 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.
- Secondary Outcome Measures
Name Time Method 2-year Radiographically Evident Progression-free Survival (REPFS). 24 months. 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).Prostate-specific Antigen (PSA) Response Rate 24 months Defined as the fraction of patients with a ≥50% reduction in serum PSA confirmed by a second serum PSA at least 3 weeks later
Median Progression-free Survival (PFS) 24 months 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.
Objective Response Rate (ORR) 24 months 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.
Median Time to Prostate-specific Antigen (PSA) Progression 24 months 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.
Prostate-specific Antigen (PSA) Doubling Time 24 months PSA doubling time = \[log (2)× t\] ÷ \[log (final PSA) - log (initial PSA)\]
Median Overall Survival (OS) 30 months 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.
Trial Locations
- Locations (51)
Paris Regional Cancer Center
🇺🇸Paris, Texas, United States
Melbourne Internal Medicine Associates
🇺🇸Melbourne, Florida, United States
Northern AZ Hematology & Oncology Assoc
🇺🇸Sedona, Arizona, United States
Florida Cancer Institute - New Hope
🇺🇸New Port Richey, Florida, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
St. Joseph Oncology, Inc.
🇺🇸St. Joseph, Missouri, United States
Hope Center
🇺🇸Terre Haute, Indiana, United States
NH Oncology-Hematology PA
🇺🇸Hooksett, New Hampshire, United States
Hematology Oncology Associates
🇺🇸Phoenix, Arizona, United States
Cancer Centers of North Carolina
🇺🇸Raleigh, North Carolina, United States
Texas Cancer Center at Medical City
🇺🇸Dallas, Texas, United States
Cancer Centers of Florida, P.A.
🇺🇸Ocoee, Florida, United States
Texas Cancer Center
🇺🇸Denton, Texas, United States
Cancer Centers of the Carolinas
🇺🇸Greenville, South Carolina, United States
Texas Cancer Center of Mesquite
🇺🇸Mesquite, Texas, United States
South Texas Cancer Center - McAllen
🇺🇸McAllen, Texas, United States
Tyler Cancer Center
🇺🇸Tyler, Texas, United States
Albany Medical Cancer Center
🇺🇸Albany, New York, United States
Texas Oncology, P.A
🇺🇸Garland, Texas, United States
Longview Cancer Center
🇺🇸Longview, Texas, United States
Interlakes Oncology Hematology, PC
🇺🇸Rochester, New York, United States
Texas Oncology, P.A. -Amarillo
🇺🇸Amarillo, Texas, United States
Mamie McFaddin Ward Cancer Center
🇺🇸Beaumont, Texas, United States
Texas Oncology - Central Austin Cancer Center
🇺🇸Austin, Texas, United States
Texas Oncology - Odessa
🇺🇸Odessa, Texas, United States
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
Allison Cancer Center
🇺🇸Midland, Texas, United States
Fairfax Northern VA Hem-Onc PC
🇺🇸Fairfax, Virginia, United States
Texas Cancer Center - Sherman
🇺🇸Sherman, Texas, United States
Onc and Hem Associates of SW VA, Inc.
🇺🇸Salem, Virginia, United States
Cancer Care Northwest-South
🇺🇸Spokane, Washington, United States
Hematology-Oncology Associates of NNJ, P
🇺🇸Morristown, New Jersey, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Cancer Care & Hematology Specialists of Chicagoland
🇺🇸Niles, Illinois, United States
Willamette Valley Cancer Center
🇺🇸Eugene, Oregon, United States
Texas Oncology, P.A.
🇺🇸Webster, Texas, United States
Yakima Valley Mem Hosp/North Star Lodge
🇺🇸Yakima, Washington, United States
Methodist Charlton Cancer Ctr.
🇺🇸Dallas, Texas, United States
El Paso Cancer Treatment Ctr
🇺🇸El Paso, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Texas Oncology Cancer Center-Sugar Land
🇺🇸Sugar Land, Texas, United States
Highline Medical Oncology
🇺🇸Burien, Washington, United States
Columbia Basin Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Puget Sound Cancer Center-Edmonds
🇺🇸Edmonds, Washington, United States
Northwest Cancer Specialists-Vancouver
🇺🇸Vancouver, Washington, United States
Rocky Mountain Cancer Center-Midtown
🇺🇸Denver, Colorado, United States
Central Indiana Cancer Centers
🇺🇸Indianapolis, Indiana, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Puget Sound Cancer Center-Seattle
🇺🇸Seattle, Washington, United States