Clinical trial NCT01156753: A Study of CDX-011 (CR011-vcMMAE) in Patients With Advanced GPNMB-expressing Breast Cancer
Official title: A Phase II, Randomized, Multicenter Study of CDX-011 (CR011-vcMMAE) in Patients With Advanced GPNMB-expressing Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: CR011-vcMMAE
locally advanced breast cancer
metastatic breast cancer
breast cancer
CDX-011
GPNMB
Targeted treatment for breast cancer
Locally advanced or metastatic breast cancer
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-07-05
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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

1. 18 years of age or older.
2. Locally advanced or metastatic breast cancer.
3. Previous treatment with at least two but no more than seven prior chemotherapy treatments for progressive, recurrent or metastatic breast cancer.
4. 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.)
5. 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:

1. Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are moderate (Grade 2) or worse in severity.
2. Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months.
3. 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.

Primary outcomes:
measure: Objective response rate
timeFrame: 6 or more weeks following treatment initiation
Secondary outcomes:
measure: Progression-free survival
timeFrame: At least 18 months following treatment initiation
measure: Adverse Events
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Long Beach
country: United States
facility: Breastlink Medical Group
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: West Coast
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology-Oncology Consultants PC
state: Georgia
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc.
state: Illinois
city: Zion
country: United States
facility: Cancer Treatment Centers of America at Midwestern Regional Medical Center
state: Illinois
city: New Orleans
country: United States
facility: Cancer Care of Louisiana
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Missoula
country: United States
facility: Montana Cancer Institute Foundation
state: Montana
city: Lake Success
country: United States
facility: Clinical Research Alliance Inc.
state: New York
city: New York
country: United States
facility: Weill Cornell Breast Center/Weill Cornell Medical College
state: New York
city: The Bronx
country: United States
facility: Montefiore-Einstein Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute/Blumenthal Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Sayre
country: United States
facility: Guthrie Clinic, Ltd.
state: Pennsylvania
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Sumter
country: United States
facility: Santee Hematology Oncology, Inc.
state: South Carolina
city: Knoxville
country: United States
facility: Center for Biomedical Research
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institution
state: Tennessee
Study officials:
References:
citation: Yardley DA, Weaver R, Melisko ME, Saleh MN, Arena FP, Forero A, Cigler T, Stopeck A, Citrin D, Oliff I, Bechhold R, Loutfi R, Garcia AA, Cruickshank S, Crowley E, Green J, Hawthorne T, Yellin MJ, Davis TA, Vahdat LT. EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer. J Clin Oncol. 2015 May 10;33(14):1609-19. doi: 10.1200/JCO.2014.56.2959. Epub 2015 Apr 6.