Clinical Trials /

Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer

NCT02492711

Description:

The purpose of this study is to determine whether patients treated with margetuximab plus chemotherapy have longer progression free survival and overall survival than patients treated with trastuzumab plus chemotherapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of HER2+ Metastatic Breast Cancer
  • Official Title: A Phase 3, Randomized Study of Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of Patients With HER2+ Metastatic Breast Cancer Who Have Received Prior Anti-HER2 Therapies and Require Systemic Treatment

Clinical Trial IDs

  • ORG STUDY ID: CP-MGAH22-04
  • NCT ID: NCT02492711

Conditions

  • HER-2 Positive Breast Cancer
  • Metastatic Neoplasm

Interventions

DrugSynonymsArms
MargetuximabMargetuximab plus chemotherapy
TrastuzumabHerceptin®Trastuzumab plus chemotherapy
CapecitabineXeloda®Margetuximab plus chemotherapy
EribulinHalaven®Margetuximab plus chemotherapy
GemcitabineGemzar ®Margetuximab plus chemotherapy
VinorelbineNavelbine®Margetuximab plus chemotherapy

Purpose

The purpose of this study is to determine whether patients treated with margetuximab plus chemotherapy have longer progression free survival and overall survival than patients treated with trastuzumab plus chemotherapy.

Detailed Description

      An evaluation of efficacy, as measured by progression-free survival (PFS) assessed by
      independent review and overall survival (OS), of margetuximab plus chemotherapy compared with
      trastuzumab plus chemotherapy in patients with advanced HER2+ breast cancer who have received
      at least 2 prior lines of anti-HER2 directed therapy in the metastatic setting, or in case of
      having received (neo)adjuvant pertuzumab, at least 1 prior line of anti-HER2 directed therapy
      in the metastatic setting, and who have received at least one, and no more than three, lines
      of therapy overall in the metastatic setting. A non-randomized sub-study cohort of
      approximately 88 patients will be enrolled to evaluate the safety of a reduced margetuximab
      infusion rate in patients receiving margetuximab either as monotherapy or in combination with
      chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Margetuximab plus chemotherapyExperimentalMargetuximab 15 mg/kg every 21 days plus Capecitabine 1000 mg/m2 BID for 14 days in a 21-day cycle or Eribulin 1.4 mg/m2 Day 1 and 8 of a 21-day cycle or Gemcitabine 1000 mg/m2 Day 1 and 8 of a 21-day cycle or Vinorelbine 25-30 mg/m2 Day 1 and 8 of a 21-day cycle
  • Margetuximab
  • Capecitabine
  • Eribulin
  • Gemcitabine
  • Vinorelbine
Trastuzumab plus chemotherapyActive ComparatorTrastuzumab 8 mg/kg loading dose then 6 mg/kg every 21 days plus Capecitabine 1000 mg/m2 BID for 14 days in a 21-day cycle or Eribulin 1.4 mg/m2 Day 1 and 8 of a 21-day cycle or Gemcitabine 1000 mg/m2 Day 1 and 8 of a 21-day cycle or Vinorelbine 25-30 mg/m2 Day 1 and 8 of a 21-day cycle
  • Trastuzumab
  • Capecitabine
  • Eribulin
  • Gemcitabine
  • Vinorelbine

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically-proven metastatic or locally-advanced relapsed/refractory HER2+ breast
             cancer based on the most recently available tumor biopsy collected from the patient.
             Tumors may be estrogen receptor (ER)/progesterone receptor (PgR) positive or negative.

          -  Have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic
             setting, or in case of having received (neo)adjuvant pertuzumab, at least 1 prior line
             of anti-HER2 directed therapy in the metastatic setting. In either case, patients must
             have received prior treatment with pertuzumab, in the (neo)adjuvant or metastatic
             setting. Prior radiotherapy, hormonal therapies, and other anti-HER2 therapies are
             allowed.

          -  Prior treatment with at least one, and no more than three, lines of therapy overall in
             the metastatic setting. Patients must have progressed on or following, the most recent
             line of therapy.

          -  Resolution of all chemotherapy or radiation-related toxicities to ≤ Grade 1

          -  Life expectancy ≥ 12 weeks

          -  Acceptable laboratory parameters

          -  Women of childbearing potential must have negative pregnancy test performed within 14
             days of randomization and on the first day of treatment. All subjects must agree to
             use an effective form of contraception for the duration of study treatment and for 7
             months after the last dose of study drug.

        Infusion sub-study prior therapy requirements: Same as above, except:

          -  Must have received 4 or more prior lines or therapy in the metastatic setting

          -  Must have received prior trastuzumab, pertuzumab, and T-DM1

        Exclusion Criteria:

          -  Known, untreated brain metastasis. Patients with signs or symptoms of brain metastasis
             must have a CT or MRI performed within 4 weeks prior to randomization to specifically
             exclude the presence of radiographically-detected brain metastases

          -  History of uncontrolled seizures within 6 months of randomization

          -  History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation

          -  History of clinically significant cardiovascular disease

          -  Clinically-significant pulmonary compromise, including a requirement for supplemental
             oxygen use to maintain adequate oxygenation

          -  Any condition that would be a contraindication to receiving trastuzumab as described
             in the approved local label or a condition that would prevent treatment with the
             physician's choice of chemotherapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) as determined by independent radiological review.
Time Frame:Approximately 41 months after the first subject is randomized; anticipated evaluation Dec 2018
Safety Issue:
Description:Overall survival of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with advanced HER2+ breast cancer.

Secondary Outcome Measures

Measure:To evaluate progression-free survival (PFS), as assessed by study investigators.
Time Frame:PFS will be evaluated approximately 41 months after the first subject is randomized.
Safety Issue:
Description:
Measure:To evaluate the objective response rate (ORR) as determined by independent radiological review.
Time Frame:ORR will be evaluated approximately 41 months after the first subject is randomized.
Safety Issue:
Description:
Measure:Infusion rate sub-study all safety
Time Frame:Cycle 2 (21 days)
Safety Issue:
Description:Incidence of all grades of infusion-related reactions

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:MacroGenics

Last Updated

December 19, 2020