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1B-13-10-A Randomized Multicenter Pivotal Study of CDX-011 (CR011-vcMMAE) in Patients with Metastatic, GPNMB Over-Expressing, Triple-Negative Breast Cancer. (The METRIC Study)

Description

This study is for females that have been diagnosed with metastatic (i.e., cancer that has spread) triple negative breast cancer (breast cancer that does not have hormone receptors or HER2) and have received no more than one prior chemotherapy treatment for advanced (locally advanced / recurrent or metastatic) breast cancer. CDX-011 (glembatumumab vedotin) is an experimental drug. CDX-011 consists of an antibody attached to a drug, MMAE, that can kill cancer cells, which is intended to work by specifically directing the drug to the cancer cell. The purpose of this study is to see whether CDX-011 is effective in treating research participants who have advanced Triple-Negative Breast Cancer (TNBC; i.e., tumors lacking expression of estrogen, progesterone and HER2 receptors) that contains GPNMB, and to examine the side effects associated with CDX-011 treatment. This study will be conducted at 100 150 centers in the US, Canada and Australia and will include approximately 300 research participants. There are three phases of study procedures, the screening phase (to make sure you are eligible to participate in the study), the treatment phase, and the follow up phase. This is an open-label, prospectively controlled, randomized study. Eligible participants will be randomized 2:1 to receive CDX-011 or capecitabine. CDX-011 will be administered on Day 1 of repeated 21 day cycles. The starting CDX-011 dose is 1.88 mg/kg, given as a 90-minute intravenous infusion. Treatment will continue until progression.Capecitabine will be orally administered on Days 1-14 of repeated 21 day cycles. The recommended capecitabine starting dose is 1250 mg/m2 twice daily. Safety will be assessed by vital sign measurements, clinical laboratory tests, ECGs, physical examinations and the incidence and severity of adverse events.Anti-tumor activity will be assessed via ORR, DOR, PFS and OS. Tumor response and progression will be defined by an independent review committee, according to RECIST 1.1 criteria.Patients will be monitored for the development of anti-CDX-011 and anti-CR011 antibodies, and whether these antibodies are neutralizing.Population PK analyses will be performed to obtain pharmacokinetic parameters and to explore the relationships between patient-specific measures of exposure and safety and activity parameters; the influence of key intrinsic factors, such as weight and gender, on variability in PK will also be evaluated. The impact of circulating GPNMB levels on pharmacokinetic parameters may also be examined.Pharmacodynamics will be evaluated via assessment of tumor tissue obtained via voluntary biopsy or re-resection. The primary efficacy analysis will be performed in accordance with the intention-to-treat principle. All randomized patients will be included in the primary efficacy analysis according to their assigned study treatment, irrespective of the actual treatment received. The primary analysis of safety will include all patients who receive at least 1 dose of study treatment.A futility analysis of ORR will be performed once 90 patients are evaluable for response (either achieve an objective response of PR or CR, discontinue treatment, or complete the 18-week disease assessment).

Phase

Phase 2/3 - for trials that are a combination of phases 2 and 3.

Inclusion and Exclusion Criteria

  • Inclusion Criteria: Among other criteria, patients must meet all of the following conditions to be eligible for the study:
  • Diagnosed with metastatic (i.e., cancer that has spread) TNBC - minimal or no expression of estrogen and progesterone receptors (ER/PR) <10% of cells positive by immunohistochemistry - HER 2 staining 0 or 1+ by IHC or copy number <4.0 signals/cell
  • Documented progression of disease based on radiographic, clinical or pathologic assessment during or subsequent to the last anticancer regimen received.
  • Breast cancer tumor confirmed to express gpNMB. This will be determined by submitting a tissue sample from the advanced (locally advanced/recurrent or metastatic) disease setting to a central laboratory for analysis.
  • Received no more than two prior chemotherapy treatments for advanced (locally advanced/recurrent or metastatic) breast cancer.
  • Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or Doxil) if clinically indicated and a taxane (eg: Taxol).
  • ECOG performance status of 0 - 1.
  • Adequate bone marrow, liver and renal function. Exclusion: Among other criteria, patients who meet any of the following conditions are NOT eligible for the study:
  • Progression/recurrence of breast cancer during or within 3 months of completion of neoadjuvant or adjuvant chemotherapy.
  • 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.
  • Previously received capecitabine and discontinued due to progression or intolerance; previously received CDX-011 or other MMAE containing agents.
  • Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary.
  • Chronic use of systemic corticosteroids.

Sites

  • California

    • USC Norris Comprehensive Cancer Center and Hospital, Los Angeles, California, 90033
    • Clinical Trials and Research Associates, Montebello, California, 90640
    • St. Jude Heritage Medical Group, Fullerton, California, 92835
    • Wilshire Oncology Medical Group, La Verne, California, 91750
    • Wilshire Oncology Medical Group, La Verne, California, 91750
    • Hematology Oncology Medical Group of Orange Country, Inc., Orange, California, 92868
    • Wellness Hematology Oncology, West Hills, California, 91307
    • Coastal Interactive Cancer Care, San Luis Obispo, California, 93401
    • Pacific Cancer Care, Salinas/Monterey, California, 93901
    • University of California San Francisco, San Francisco, California, 94115
    • University of California Davis Medical Center, Sacramento, California, 95817
    • Kaiser Permaente, Vallejo, California, 94589
  • Arizona

    • Yuma Regional Cancer Center, Yuma, Arizona, 85364
    • Arizona Center for Cancer Care, Glendale, Arizona, 85306
    • Arizona Cancer Research Alliance, Scottsdale, Arizona, 85251
    • Arizona Cancer Center, Tucson, Arizona, 85724
  • Oregon

    • Bay Area Hospital, Coos Bay, Oregon, 97420
    • Oregon Health and Science University, Beaverton, Oregon, 97006
  • Montana

    • Montana Cancer Specialists, Missoula, Montana, 59802
  • Texas

    • Texas Tech University Health Sciences Center, Lubbock, Texas, 79430
    • Oncology Hematology Consultants PA, Forth Worth, Texas, 76104
    • Baylor Collete of Medicine, Houston, Texas, 77030
    • University of Texas Health Science Center at Houston, Houston, Texas, 77030
  • Washington

    • Swedish Cancer Institute, Seattle, Washington, 98104
  • Oklahoma

    • Mercy Clinic of Oklahoma, Oklahoma City, Oklahoma, 73120
  • Nebraska

    • Missouri Valley Cancer Consortium, Omaha, Nebraska, 68106
  • Arkansas

    • University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205
  • Missouri

    • Columbia Comprehensive Cancer Care Clinic, Jefferson City, Missouri, 65109
    • St John's Mercy Medical Center, St. Louis, Missouri, 63141
    • Washington University Dept of Oncology, St. Louis, Missouri, 63110
    • Washington University Dept of Oncology, St. Louis, Missouri, 63110
  • Iowa

    • Cedar Valley Medical Specialists, Waterloo, Iowa, 50701
  • Tennessee

    • The Jones Clinic, PC, Germantown, Tennessee, 38138
    • Sarah Cannon Cancer Center, Nashville, Tennessee, 37203
    • Chattanooga Oncology Hematology Associates, Chattanooga, Tennessee, 37404
    • Associates in Oncology and Hematology, Chattanooga, Tennessee, 37421
  • Louisiana

    • Oschner Medical Center, New Orleans, Louisiana, 70121
    • Hematology and Oncology Specialists, Marrero, Louisiana, 70072
  • Mississippi

    • North Mississippi Hematology and Oncology Associates, Tupelo, Mississippi, 38801
  • Illinois

    • Carle Cancer Center, Urbana, Illinois, 61801
    • Midwestern Regional Medical Center, Zion, Illinois, 60099
    • Orchard Healthcare Research Inc., Skokie, Illinois, 60077
    • Ingalis Memorial Hospital, Harvey, Illinois, 60426
    • Edward H. Kaplan and Associates, Skokie, Illinois, 60076
    • University of Chicago, Chicago, Illinois, 60637
    • Illinois CancerCare, Peoria, Illinois, 60615
  • Alabama

    • Southern Cancer Center, Mobile, Alabama, 36608
    • University of South Alabama Cancer Research Insititute, Mobile, Alabama, 36604
    • University of Alabama at Birmingham, Birmingham, Alabama, 35294
    • Alabama Oncology, Birmingham, Alabama, 35211
  • Ohio

    • Signal Point Clinical Research Center, LLC, Middletown, Ohio, 45042
    • Oncology Hematology Care, Cincinnati, Ohio, 45242
  • Georgia

    • Northwest Georgia Oncology Centers P.C., Marietta, Georgia, 30060
    • Piedmont Cancer Institute, Atlanta, Georgia, 30318
    • Winship Cancer Institute, Emory University, Atlanta, Georgia, 30322
    • Georgia Cancer Specialists Clinic, Atlanta, Georgia, 30341
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