Clinical trial NCT00661492: Mitoxantrone ± Cetuximab 2nd Line Androgen Independent Prostate Cancer (AIPC)
Official title: A Randomized Phase II Study of Mitoxantrone vs. Mitoxantrone With Cetuximab in Metastatic Androgen Independent Prostate Cancer (AIPC) Previously Treated With Docetaxel-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Androgen-independent Prostate Cancer
Keywords: Androgen-independent prostate cancer(AIPC)
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
name: Oregon Health and Science University
First posted: 2008-04-18
Enrollment: 115
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the prostate. Note: Patients may have either measurable or non-measurable disease.
* Radiographic evidence of regional or distant metastases
* Current evidence of progression (by PSA and/or imaging studies) despite standard hormonal therapy.
* 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.
* 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).
* 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).
* 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
* ECOG performance status
* Laboratory criteria for entry:

  * absolute neutrophil count
  * platelets
  * bilirubin
  * AST or ALT
* Life expectancy greater than 3 months
* Age greater than or equal to 18 years
* Agree to use contraceptives while on study if sexually active, and for 2 months after the last dose of study drug.
* Has signed a Patient Informed Consent Form
* Has signed a Patient Authorization Form

Exclusion Criteria:

* 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

Primary outcomes:
measure: Median Time to Progression (TTP)
timeFrame: 24 months
Secondary outcomes:
measure: 2-year Radiographically Evident Progression-free Survival (REPFS).
timeFrame: 24 months.
measure: Objective Response Rate (ORR)
timeFrame: 24 months
measure: Median Time to Prostate-specific Antigen (PSA) Progression
timeFrame: 24 months
measure: Prostate-specific Antigen (PSA) Response Rate
timeFrame: 24 months
measure: Prostate-specific Antigen (PSA) Doubling Time
timeFrame: 24 months
measure: Median Progression-free Survival (PFS)
timeFrame: 24 months
measure: Median Overall Survival (OS)
timeFrame: 30 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Hematology Oncology Associates
state: Arizona
city: Sedona
country: United States
facility: Northern AZ Hematology & Oncology Assoc
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Midtown
state: Colorado
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute - New Hope
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Terre Haute
country: United States
facility: Hope Center
state: Indiana
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: St. Joseph
country: United States
facility: St. Joseph Oncology, Inc.
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Hooksett
country: United States
facility: NH Oncology-Hematology PA
state: New Hampshire
city: Morristown
country: United States
facility: Hematology-Oncology Associates of NNJ, P
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Cancer Center
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology Hematology, PC
state: New York
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina
state: North Carolina
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Amarillo
country: United States
facility: Texas Oncology, P.A. -Amarillo
state: Texas
city: Arlington
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Austin
country: United States
facility: Texas Oncology - Central Austin Cancer Center
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: Methodist Charlton Cancer Ctr.
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Denton
country: United States
facility: Texas Cancer Center
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Ctr
state: Texas
city: Ft. Worth
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Garland
country: United States
facility: Texas Oncology, P.A
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center - McAllen
state: Texas
city: Mesquite
country: United States
facility: Texas Cancer Center of Mesquite
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center
state: Texas
city: Odessa
country: United States
facility: Texas Oncology - Odessa
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center - Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center-Sugar Land
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Webster
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Fairfax
country: United States
facility: Fairfax Northern VA Hem-Onc PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Salem
country: United States
facility: Onc and Hem Associates of SW VA, Inc.
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Edmonds
country: United States
facility: Puget Sound Cancer Center-Edmonds
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center-Seattle
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest-South
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists-Vancouver
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Mem Hosp/North Star Lodge
state: Washington
Study officials:
affiliation: Virginia Oncology Associates/US Oncology
name: Mark T. Fleming, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fleming MT, Sonpavde G, Kolodziej M, Awasthi S, Hutson TE, Martincic D, Rastogi A, Rousey SR, Weinstein RE, Galsky MD, Berry WR, Wang Y, Boehm KA, Asmar L, Rauch MA, Beer TM. Association of rash with outcomes in a randomized phase II trial evaluating cetuximab in combination with mitoxantrone plus prednisone after docetaxel for metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 2012 Mar;10(1):6-14. doi: 10.1016/j.clgc.2011.11.003.