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

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ClinicalTrials.gov Identifier: NCT01997333
Recruitment Status : Completed
First Posted : November 28, 2013
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics

Brief Summary:
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), 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 or disease Intervention/treatment Phase
Metastatic gpNMB Over-expressing Triple Negative Breast Cancer Drug: CDX-011 Drug: Capecitabine Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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 efficacy 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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 327 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Study Start Date : November 2013
Actual Primary Completion Date : November 30, 2017
Actual Study Completion Date : August 7, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Evaluated every 6 - 9 weeks following treatment initiation ]
    PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Evaluated every 6 - 9 weeks following treatment initiation ]
    ORR is defined as the proportion of patients who achieve best overall response of complete or partial response according to RECIST 1.1.

  2. Duration of Response (DOR) [ Time Frame: Evaluated every 6 - 9 weeks following treatment initiation ]
  3. Overall Survival (OS) [ Time Frame: During treatment and 3 months from end of treatment through end of study or approximately up to 5 years. ]
  4. 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) ]
    The percentage of patients experiencing one or more adverse events will be summarized by treatment arm, relationship to study drug, and severity.

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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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) 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
  2. Documented progression of disease based on radiographic, clinical or pathologic assessment during or subsequent to the last anticancer regimen received.
  3. 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.
  4. Received no more than two prior chemotherapy treatments for advanced (locally advanced/recurrent or metastatic) breast cancer.
  5. Prior chemotherapy treatment must have contained an anthracycline (e.g. doxorubicin or Doxil) if clinically indicated and a taxane (eg: 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 3 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.
  5. Previously received capecitabine and discontinued due to progression or intolerance; previously received CDX-011 or other MMAE containing agents.
  6. Active systemic infection requiring treatment. Infection controlled by oral therapy will not be exclusionary.
  7. Chronic use of systemic corticosteroids.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01997333


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Sponsors and Collaborators
Celldex Therapeutics

Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT01997333     History of Changes
Other Study ID Numbers: CDX011-04
First Posted: November 28, 2013    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: November 2017

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

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
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs