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

NCT ID: NCT00661492

Last Updated: 2016-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2011-06-30

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.

Conditions

Androgen-independent Prostate Cancer

Keywords

Androgen-independent prostate cancer(AIPC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Erbitux (cetuximab) and Novantrone (mitoxantrone)

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: DRUG

Erbitux (cetuximab) IV over 2 hours (loading dose) on Day 1 (Cycle 1 only), followed by Erbitux (cetuximab) IV over 1 hour weekly thereafter

Mitoxantrone

Intervention Type: DRUG

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

Arm 2

Novantrone (mitoxantrone)

Group Type: EXPERIMENTAL

Mitoxantrone

Intervention Type: DRUG

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

Interventions

cetuximab

Erbitux (cetuximab) IV over 2 hours (loading dose) on Day 1 (Cycle 1 only), followed by Erbitux (cetuximab) IV over 1 hour weekly thereafter

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Erbitux; Novantrone

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

US Oncology Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark T. Fleming, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Oncology Associates/US Oncology

Locations

Hematology Oncology Associates

Phoenix, Arizona, United States

Northern AZ Hematology & Oncology Assoc

Sedona, Arizona, United States

Rocky Mountain Cancer Center-Midtown

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

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, United States

Missouri Cancer Associates

Columbia, Missouri, United States

St. Joseph Oncology, Inc.

Saint Joseph, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

NH Oncology-Hematology PA

Hooksett, New Hampshire, United States

Hematology-Oncology Associates of NNJ, P

Morristown, New Jersey, United States

Albany Medical Cancer Center

Albany, New York, United States

Interlakes Oncology Hematology, PC

Rochester, New York, United States

Cancer Centers of North Carolina

Raleigh, North Carolina, United States

Greater Dayton Cancer Center

Kettering, Ohio, United States

Willamette Valley Cancer Center

Eugene, Oregon, United States

Oregon Health & Science University

Portland, Oregon, United States

Cancer Centers of the Carolinas

Greenville, South Carolina, 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

Texas Cancer Center at Medical City

Dallas, Texas, United States

Texas Oncology, P.A.

Dallas, Texas, United States

Methodist Charlton Cancer Ctr.

Dallas, Texas, United States

Texas Oncology, P.A.

Dallas, Texas, United States

Texas Cancer Center

Denton, Texas, United States

El Paso Cancer Treatment Ctr

El Paso, Texas, United States

Texas Oncology, P.A.

Fort Worth, Texas, United States

Texas Oncology, P.A

Garland, Texas, United States

Longview Cancer Center

Longview, Texas, United States

South Texas Cancer Center - McAllen

McAllen, Texas, United States

Texas Cancer Center of Mesquite

Mesquite, Texas, United States

Allison Cancer Center

Midland, Texas, United States

Texas Oncology - Odessa

Odessa, Texas, United States

Paris Regional Cancer Center

Paris, Texas, United States

Texas Cancer Center - Sherman

Sherman, Texas, United States

Texas Oncology Cancer Center-Sugar Land

Sugar Land, Texas, United States

Tyler Cancer Center

Tyler, Texas, United States

Texas Oncology, P.A.

Webster, Texas, United States

Fairfax Northern VA Hem-Onc PC

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Onc and Hem Associates of SW VA, Inc.

Salem, Virginia, United States

Highline Medical Oncology

Burien, Washington, United States

Puget Sound Cancer Center-Edmonds

Edmonds, Washington, United States

Columbia Basin Hematology and Oncology

Kennewick, Washington, United States

Puget Sound Cancer Center-Seattle

Seattle, Washington, United States

Cancer Care Northwest-South

Spokane, Washington, United States

Northwest Cancer Specialists-Vancouver

Vancouver, Washington, United States

Yakima Valley Mem Hosp/North Star Lodge

Yakima, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 22340631 (View on PubMed)

Other Identifiers

06-118

Identifier Type: -

Identifier Source: org_study_id