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

Breast Cancer Clinical Trial

— EMERGE  

Official title:

A Phase II, Randomized, Multicenter Study of CDX-011 (CR011-vcMMAE) in Patients With Advanced GPNMB-expressing Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01156753
• Other study ID #: CDX011-03
• Status: Completed
• Phase: Phase 2
• First received: June 30, 2010
• Last updated: June 26, 2017
• Start date: July 2010
• Est. completion date: November 2012

Study information

• Verified date: June 2017
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: November 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• CDX-011
CDX-011 (1.88 mg/kg) administered as an intravenous infusion on Day 1 of each 21 day cycle.
• "Investigator's Choice" chemotherapy
Any of the following single-agent chemotherapy may be given at the discretion of the investigator, with a cycle length not to exceed four weeks: Capecitabine, Vinorelbine, Gemcitabine, Docetaxel, Paclitaxel, Albumin-bound paclitaxel, Doxorubicin HCL, Liposomal doxorubicin, Ixabepilone and Eribulin.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate	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.	6 or more weeks following treatment initiation
Secondary	Progression-free survival	Progression-free survival is defined as the time from randomization to the earlier of disease progression or death due to any cause.	At least 18 months following treatment initiation
Secondary	Adverse Events	The number and percentage of patients experiencing one or more adverse events will be summarized by treatment arm, relationship to study drug, and severity.	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)