A Study of CDX-011 (CR011-vcMMAE) in Patients With Advanced GPNMB-expressing Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer

Interventions: Drug: CDX-011
Drug: "Investigator's Choice" chemotherapy

Registration Number: NCT01156753

Lead Sponsor: Celldex Therapeutics

Brief Summary: The main purpose of this study is to see whether CDX-011 is effective in treating patients who have advanced breast cancer that makes a protein called glycoprotein NMB (GPNMB), and who have already received (or were not candidates for) all available approved therapies for their breast cancer. This study will also further characterize the safety of CDX-011 treatment in this patient population.

Detailed Description: CDX-011 consists of an antibody attached to a drug, monomethyl auristatin E (MMAE), that can kill cancer cells. The antibody delivers the drug to cancer cells by attaching to a protein called glycoprotein NMB (GPNMB) that is expressed on the cancer cell. The MMAE is then released inside of the cell, where it interferes with cell growth and may lead to cell death.

This study will examine the effectiveness and safety of CDX-011 in patients with advanced breast cancer that makes the GPNMB protein. To better assess this, the effect of CDX-011 will be compared to treatment with currently available cancer chemotherapy.

Eligible patients who enroll in the study will be randomly assigned by chance to receive treatment with CDX-011 or with a chemotherapy chosen by their study doctor from a list of currently available drugs ("Investigator's Choice" chemotherapy). For each three patients enrolled, two will receive CDX-011 and one will receive treatment with "Investigator's Choice". Patients initially assigned to "Investigator's Choice" chemotherapy may be offered treatment with CDX-011 if their cancer worsens during this initial treatment.

All patients enrolled in the study will be closely monitored to determine if their cancer is responding to treatment, and for any side effects that may occur.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 120

Inclusion Criteria

Among other criteria, patients must meet all of the following conditions to be eligible for the study:

18 years of age or older.
Locally advanced or metastatic breast cancer.
Previous treatment with at least two but no more than seven prior chemotherapy treatments for progressive, recurrent or metastatic breast cancer.
Unless not a candidate for these agents, prior therapies must have included a taxane, an anthracycline, and capecitabine, as well as trastuzumab and lapatinib for patients whose tumors are positive for the human epidermal growth factor receptor 2 (HER2). (Patients who received incomplete courses of therapy with these agents due to intolerance will be eligible.)
Breast cancer tumor confirmed to express GPNMB. This will be determined by submitting a tissue sample (obtained during a diagnostic biopsy or surgery) to a central laboratory for analysis.

Exclusion Criteria

Among other criteria, patients who meet any of the following conditions are NOT eligible for the study:

Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are moderate (Grade 2) or worse in severity.
Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months.
Significant cardiovascular disease or any other underlying medical condition that, in the Investigator's opinion, will make the administration of study treatment (CDX-011 or chemotherapy) hazardous or would obscure the interpretation of side effects.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CDX-011	CDX-011	-
"Investigator's Choice" chemotherapy	"Investigator's Choice" chemotherapy	-

Primary Outcome Measures

Name	Time	Method
Objective response rate	6 or more weeks following treatment initiation	The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guideline.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival	At least 18 months following treatment initiation	Progression-free survival is defined as the time from randomization to the earlier of disease progression or death due to any cause.
Adverse Events	Usually following at least 1 cycle of study treatment (1 dose of CDX-011 or "Investigator's Choice" chemotherapy and 3 to 4 weeks of follow-up)	The number and percentage of patients experiencing one or more adverse events will be summarized by treatment arm, relationship to study drug, and severity.

Trial Locations

Locations (24): USC/Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
The Angeles Clinic and Research Institute
🇺🇸
Los Angeles, California, United States
Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Florida Cancer Specialists
🇺🇸
West Coast, Florida, United States
Breastlink Medical Group
🇺🇸
Long Beach, California, United States
Montana Cancer Institute Foundation
🇺🇸
Missoula, Montana, United States
Oncology Hematology Care
🇺🇸
Cincinnati, Ohio, United States
Guthrie Clinic, Ltd.
🇺🇸
Sayre, Pennsylvania, United States
The University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸
Birmingham, Alabama, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸
San Francisco, California, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Sarah Cannon Research Institution
🇺🇸
Nashville, Tennessee, United States
Cancer Care of Louisiana
🇺🇸
New Orleans, Louisiana, United States
Cancer Treatment Centers of America at Midwestern Regional Medical Center
🇺🇸
Zion, Illinois, United States
Georgia Cancer Specialists
🇺🇸
Atlanta, Georgia, United States
Orchard Healthcare Research Inc.
🇺🇸
Skokie, Illinois, United States
Montefiore-Einstein Cancer Center
🇺🇸
The Bronx, New York, United States
Weill Cornell Breast Center/Weill Cornell Medical College
🇺🇸
New York, New York, United States
Clinical Research Alliance Inc.
🇺🇸
Lake Success, New York, United States
Peachtree Hematology-Oncology Consultants PC
🇺🇸
Atlanta, Georgia, United States
Center for Biomedical Research
🇺🇸
Knoxville, Tennessee, United States
Levine Cancer Institute/Blumenthal Cancer Center
🇺🇸
Charlotte, North Carolina, United States
Santee Hematology Oncology, Inc.
🇺🇸
Sumter, South Carolina, United States
South Carolina Oncology Associates
🇺🇸
Columbia, South Carolina, United States