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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
Results First Posted : March 8, 2019
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics

Tracking Information
First Submitted Date  ICMJE November 18, 2013
First Posted Date  ICMJE November 28, 2013
Results First Submitted Date  ICMJE November 30, 2018
Results First Posted Date  ICMJE March 8, 2019
Last Update Posted Date March 8, 2019
Study Start Date  ICMJE November 2013
Actual Primary Completion Date November 30, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
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. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or progression in a non-target lesion, or the appearance of new lesions. The primary analysis of PFS was based on PFS events determined retrospectively by the central independent review committee, blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: November 27, 2013)
  • Objective Response Rate (ORR) [ Time Frame: Six 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.
  • Progression Free Survival (PFS) [ Time Frame: At least 18 months following treatment initiation. ]
    PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause.
Change History Complete list of historical versions of study NCT01997333 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
  • Objective Response Rate (ORR) [ Time Frame: Evaluated every 6 - 9 weeks following treatment initiation ]
    ORR is defined as the percentage of patients who achieve best overall response of complete or partial response. The analysis of ORR was based on ORR events determined retrospectively by the central independent review committee, blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Complete Response (CR) = Disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
  • Duration of Response [ Time Frame: Evaluated every 6 - 9 weeks following treatment initiation ]
    Duration of response (DOR) is the number of months from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented. The analysis of DOR was determined retrospectively by the central independent review committee,blinded to treatment assignment and investigator assessments according to RECIST 1.1 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Complete Response (CR) = Disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
  • Overall Survival [ Time Frame: During treatment and 3 months from end of treatment through end of study or approximately up to 5 years. ]
    Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.
  • 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.
  • Pharmacokinetics (PK) [ Time Frame: Following 1 dose of CDX-011. ]
    Concentration of the antibody drug conjugate (ADC), total antibody (TA) and free MMAE will be determined.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2013)
  • Duration of Response (DOR) [ Time Frame: At least 18 months following treatment initiation ]
  • Overall Survival (OS) [ Time Frame: During treatment and 3 months from end of treatment through end of study or approximately up to 5 years. ]
  • 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.
  • Pharmacokinetic (PK) [ Time Frame: Following 1 dose of CDX-011. ]
    Concentration of the antibody-drug conjugate, total antibody and free MMAE will be determined.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Glembatumumab Vedotin (CDX-011) in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer
Official Title  ICMJE A Randomized Multicenter Pivotal Study of CDX-011 (CR011-vcMMAE)in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (The METRIC Study)
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic gpNMB Over-expressing Triple Negative Breast Cancer
Intervention  ICMJE
  • Drug: CDX-011
  • Drug: Capecitabine
Study Arms  ICMJE
  • Active Comparator: Capecitabine
    Capecitabine will be administered on Days 1 through 14 of each 21 day cycle.
    Intervention: Drug: Capecitabine
  • Experimental: Drug: CDX-011
    CDX-011 administered as an intravenous infusion on Day 1 of each 21 day cycle.
    Intervention: Drug: CDX-011
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 29, 2017)
327
Original Estimated Enrollment  ICMJE
 (submitted: November 27, 2013)
300
Actual Study Completion Date  ICMJE August 7, 2018
Actual Primary Completion Date November 30, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries Austria
 
Administrative Information
NCT Number  ICMJE NCT01997333
Other Study ID Numbers  ICMJE CDX011-04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celldex Therapeutics
Study Sponsor  ICMJE Celldex Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Celldex Therapeutics
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP