Mitoxantrone ± Cetuximab 2nd Line Androgen Independent Prostate Cancer (AIPC)

Androgen-independent Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00661492
• Other study ID #: 06-118
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 4, 2008
• Last updated: April 6, 2010
• Start date: May 2008
• Est. completion date: May 2010

Study information

• Verified date: April 2010
• Source: US Oncology Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Androgen-independent Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Erbitux (cetuximab) and Novantrone (mitoxantrone)
Arm 1: Erbitux (cetuximab) IV over 2 hours (loading dose) on Day 1 (Cycle 1 only), followed by Erbitux (cetuximab) IV over 1 hour weekly thereafter and Novantrone (mitoxantrone) IV Day 1 + Prednisone QD for ten (10) 21-day cycles
• Novantrone (mitoxantrone)
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

Locations

Country	Name	City	State
United States	Albany Medical Cancer Center	Albany	New York
United States	Texas Oncology, P.A. -Amarillo	Amarillo	Texas
United States	Texas Oncology, P.A.	Arlington	Texas
United States	Texas Oncology - Central Austin Cancer Center	Austin	Texas
United States	Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Highline Medical Oncology	Burien	Washington
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Methodist Charlton Cancer Ctr.	Dallas	Texas
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Texas Cancer Center	Denton	Texas
United States	Rocky Mountain Cancer Center-Midtown	Denver	Colorado
United States	Puget Sound Cancer Center-Edmonds	Edmonds	Washington
United States	El Paso Cancer Treatment Ctr	El Paso	Texas
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Fairfax Northern VA Hem-Onc PC	Fairfax	Virginia
United States	Texas Oncology, P.A.	Ft. Worth	Texas
United States	Texas Oncology, P.A	Garland	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	NH Oncology-Hematology PA	Hooksett	New Hampshire
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Columbia Basin Hematology and Oncology	Kennewick	Washington
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Longview Cancer Center	Longview	Texas
United States	South Texas Cancer Center - McAllen	McAllen	Texas
United States	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	Texas Cancer Center of Mesquite	Mesquite	Texas
United States	Allison Cancer Center	Midland	Texas
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Hematology-Oncology Associates of NNJ, P	Morristown	New Jersey
United States	Florida Cancer Institute - New Hope	New Port Richey	Florida
United States	Cancer Care & Hematology Specialists of Chicagoland	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Ocala Oncology Center	Ocala	Florida
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Texas Oncology - Odessa	Odessa	Texas
United States	Paris Regional Cancer Center	Paris	Texas
United States	Hematology Oncology Associates	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Cancer Centers of North Carolina	Raleigh	North Carolina
United States	Interlakes Oncology Hematology, PC	Rochester	New York
United States	Onc and Hem Associates of SW VA, Inc.	Salem	Virginia
United States	Puget Sound Cancer Center-Seattle	Seattle	Washington
United States	Northern AZ Hematology & Oncology Assoc	Sedona	Arizona
United States	Texas Cancer Center - Sherman	Sherman	Texas
United States	Cancer Care Northwest-South	Spokane	Washington
United States	St. Joseph Oncology, Inc.	St. Joseph	Missouri
United States	Texas Oncology Cancer Center-Sugar Land	Sugar Land	Texas
United States	Hope Center	Terre Haute	Indiana
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists-Vancouver	Vancouver	Washington
United States	Texas Oncology, P.A.	Webster	Texas
United States	Yakima Valley Mem Hosp/North Star Lodge	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
US Oncology Research	ImClone LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		approximately 2 years	No
Secondary	Time to radiographically evident disease progression, response rate in measurable disease, time to PSA, PSA response rate, PSA doubling time, overall survival, response rate attributable to the addition of Erbitux and Novatrone		approximately 2 years	No