Study of Glembatumumab Vedotin (CDX-011) in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (METRIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Celldex Therapeutics
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics
ClinicalTrials.gov Identifier:
NCT01997333
First received: November 18, 2013
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

The main purpose of this study is to see whether CDX-011 (glembatumumab vedotin, an antibody-drug conjugate) is effective in treating patients who have advanced Triple-Negative Breast Cancer (TNBC; i.e., tumors lacking expression of estrogen, progesterone and HER2 receptors), and whose tumor cells make a protein called glycoprotein NMB (gpNMB), which CDX-011 binds to. The study will also further characterize the safety of CDX-011 treatment in this patient population.


Condition Intervention Phase
Metastatic gpNMB Over-expressing Triple Negative Breast Cancer.
Drug: CDX-011
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Multicenter Pivotal Study of CDX-011 (CR011-vcMMAE)in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (The METRIC Study)

Resource links provided by NLM:


Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Six weeks following treatment initiation. ] [ Designated as safety issue: No ]
    ORR is defined as the proportion of patients who achieve best overall response of complete or partial response according to RECIST 1.1.

  • Progression Free Survival (PFS) [ Time Frame: At least 18 months following treatment initiation. ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause.


Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: At least 18 months following treatment initiation ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: During treatment and 3 months from end of treatment through end of study or approximately up to 5 years. ] [ Designated as safety issue: No ]
  • Adverse Events (AE) [ Time Frame: Usually following at least 1 cycle of study treatment (1 dose of CDX-011 or capecitabine and until discontinuation of follow-up) ] [ Designated as safety issue: Yes ]
    The percentage of patients experiencing one or more adverse events will be summarized by treatment arm, relationship to study drug, and severity.

  • Pharmacokinetic (PK) [ Time Frame: Following 1 dose of CDX-011. ] [ Designated as safety issue: Yes ]
    Concentration of the antibody-drug conjugate, total antibody and free MMAE will be determined.


Estimated Enrollment: 300
Study Start Date: November 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Capecitabine
Capecitabine will be administered on Days 1 through 14 of each 21 day cycle.
Drug: Capecitabine
Experimental: Drug: CDX-011
CDX-011 administered as an intravenous infusion on Day 1 of each 21 day cycle.
Drug: CDX-011

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 TNBC that makes the gpNMB protein. The effect of CDX-011 will be compared to treatment with capecitabine.

Eligible patients who enroll in the study will be randomly assigned (by chance) to receive treatment with CDX-011 or with capecitabine. For every three patients enrolled, two will receive CDX-011 and one will receive treatment with capecitabine. 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  1. Diagnosed with metastatic (i.e., cancer that has spread) triple negative (does not have hormone receptors ER or PR or HER2) breast cancer.
  2. 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.
  3. Received no more than two prior chemotherapy treatments for advanced (locally advanced/recurrent or metastatic) breast cancer.
  4. Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or Doxil) and a taxane (eg: Taxol).
  5. Breast cancer must be resistant or intolerant to treatment containing taxane (e.g. Taxol).
  6. ECOG performance status of 0 - 1.
  7. 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:

  1. Progression/recurrence of breast cancer during or within 6 months of completion of neoadjuvant or adjuvant chemotherapy.
  2. Ongoing neuropathy or other chemotherapy or radiation-related toxicities that are moderate (Grade 2) or worse in severity.
  3. Known brain metastases, unless previously treated and asymptomatic for 2 months and not progressive in size or number for 2 months.
  4. Significant cardiovascular disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01997333

Contacts
Contact: Celldex Therapeutics info@celldex.com

  Show 72 Study Locations
Sponsors and Collaborators
Celldex Therapeutics
  More Information

No publications provided

Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT01997333     History of Changes
Other Study ID Numbers: CDX011-04
Study First Received: November 18, 2013
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board
Canada: Health Canada
Australia: Department of Health and Aging Therapeutic Goods Administration

Keywords provided by Celldex Therapeutics:
Metastatic Breast Cancer
Locally advanced breast cancer
Breast cancer
Targeted treatment for breast cancer
Breast Neoplasms
Triple negative
Estrogen
Progesterone
HER2 receptors
Antibody-drug-conjugate
CDX-011
gpNMB
METRIC
Glembatumumab vedotin

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014