Clinical Trials /

MARGetuximab Or Trastuzumab (MARGOT)

NCT04425018

Description:

The purpose of this study is to determine how well participants with stage II-III HER2-positive breast cancer respond to pre-operative treatment using one of two different combinations of drugs. Drugs and Combinations used: - Paclitaxel, Pertzumab and Margetuximab - Paclitaxel, Pertzumab and Trastuzumab (Herceptin)

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MARGetuximab Or Trastuzumab (MARGOT)
  • Official Title: MARGetuximab Or Trastuzumab (MARGOT): A Phase II Study Comparing Neoadjuvant Paclitaxel/Margetuximab/Pertuzumab to Paclitaxel/Trastuzumab/Pertuzumab in Patients With Stage II-III HER2-positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20-068
  • NCT ID: NCT04425018

Conditions

  • Breast Cancer
  • Stage II Breast Cancer
  • Stage III Breast Cancer
  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
PaclitaxelTaxol, OnxalPaclitaxel + Pertuzumab + Margetuximab
PertuzumabPerjetaPaclitaxel + Pertuzumab + Margetuximab
MargetuximabPaclitaxel + Pertuzumab + Margetuximab
TrastuzumabHerceptin, Kanjinti, Ogivri, HerzumaPaclitaxel + Pertuzumab + Trastuzumab

Purpose

The purpose of this study is to determine how well participants with stage II-III HER2-positive breast cancer respond to pre-operative treatment using one of two different combinations of drugs. Drugs and Combinations used: - Paclitaxel, Pertzumab and Margetuximab - Paclitaxel, Pertzumab and Trastuzumab (Herceptin)

Detailed Description

      This is a randomized open-label phase II trial comparing paclitaxel/margetuximab/pertuzumab
      (TMP) to paclitaxel/trastuzumab/pertuzumab (THP) in patients with anatomic stage II-III HER2
      positive breast cancer.

        -  The research study procedures include screening for eligibility and study treatment
           including laboratory evaluations, two mandatory research biopsies and follow up visits.

        -  Participants will be randomized, which means randomly assigned, to one of two treatment
           arms. The treatment arms in this study and the names of the study drugs in each arm are:

             -  Arm A: Paclitaxel, Pertzumab and Margetuximab

             -  Arm B: Paclitaxel, Pertzumab and Trastuzumab

      Participants will receive study treatment for 12 weeks prior to surgery and will be followed
      for 10 years after surgery. After surgery, some participants will continue to receive the
      study drug margetuximab for a year in total, if they respond very well to the first 12 weeks
      of treatment with margetuximab.

      It is expected that about 171 people will take part in this research study.

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug combination to learn whether the drug
      combination works in treating a specific disease. "Investigational" means that the drug
      combination is being studied.

      The FDA (the U.S. Food and Drug Administration) has approved paclitaxel, trastuzumab
      (Herceptin), and pertuzumab as part of a pre-operative treatment option for stage II-III
      HER2-positive breast cancer.

      The use of margetuximab has not been approved by the FDA, for treatment of HER2-positive
      breast cancer, or any other type of cancer. In other clinical studies, this drug has
      prevented or slowed the growth of breast cancer.

      Previous studies also suggest that margetuximab could be more or equally as effective as
      trastuzumab for patients with certain immune system features and stage II-III HER2-positive
      breast cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Paclitaxel + Pertuzumab + MargetuximabExperimentalThe research study procedures include screening for eligibility and study treatment including laboratory evaluations, two mandatory research biopsies and follow up visits.Cycle=21 days Paclitaxel- via IV, Day 1,8,15 of each cycle Margetuximab via IV, Day 1 of each cycle Pertuzumab via IV, Day 1 of each cycle
  • Paclitaxel
  • Pertuzumab
  • Margetuximab
Paclitaxel + Pertuzumab + TrastuzumabExperimentalThe research study procedures include screening for eligibility and study treatment including laboratory evaluations, two mandatory research biopsies and follow up visits.Cycle=21 days Paclitaxel- via IV, Day 1,8,15 of each cycle Pertuzumab via IV, Day 1 of each cycle Trastuzumab via IV, Day 1 of each cycle
  • Paclitaxel
  • Pertuzumab
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Stage II or III (according to AJCC cancer staging manual anatomic staging table, 8th
             edition) histologically confirmed invasive carcinoma of the breast. A minimum tumor
             size of 1.5 cm (in breast mass or axillary lymph node) determined by physical exam or
             imaging (whichever is larger) is required. Patients with inflammatory breast carcinoma
             (T4d) are NOT eligible.

          -  Centrally confirmed to have a low affinity CD16 germline genotype (FF or FV)

          -  HER-2 positive by 2018 American Society of Clinical Oncology/College of American
             Pathologists criteria, as assessed by standard institutional guidelines (central
             testing is not required).

          -  ER/PR determination is required. ER- and PR-assays should be performed by
             immunohistochemical methods according to standard institutional guidelines

          -  Bilateral breast cancers are allowed as long as both cancers are HER2-positive (as
             defined in 3.1.2), or the contralateral cancer is a <1 cm, ER+ tumor.

          -  Patients with multifocal or multicentric disease are eligible if the treating
             investigator has determined the patient should be treated as HER2-positive.

          -  Breast imaging should include dedicated ultrasound of the ipsilateral axilla. For
             subjects with a clinically positive axilla based on exam or imaging, a fine needle
             aspiration or core biopsy procedure will be performed to determine the presence of
             metastatic disease in the lymph nodes (though lymph node sampling procedure need not
             be resulted prior to patient's registration on trial, as long as all other eligibility
             are met).

          -  Men and women (with any menopausal status) ≥18 years of age are eligible.

          -  ECOG performance status 0 or 1

          -  Required laboratory values demonstrating adequate organ function:

               -  ANC ≥ 1000/mm3

               -  Hemoglobin ≥ 9 g/dl

               -  Platelets ≥ 100,000/mm3

               -  Serum creatinine < 1.5 x ULN (institutional) OR calculated GFR ≥ 60mL/min

               -  Total bilirubin ≤ 1.5 x ULN (institutional). For patients with Gilbert Syndrome,
                  the direct bilirubin should be within the institutional normal range OR total
                  bilirubin ≤ 2.0 mg/dL.

               -  AST and ALT ≤ 2.5x ULN (institutional) Left ventricular ejection fraction (LVEF)
                  ≥ 50%.

          -  Women of childbearing potential must have a negative serum pregnancy test within 14
             days of registration. Childbearing potential is defined as: those who have not been
             surgically sterilized and/or have had a menstrual period in the past 12 months

          -  Women of childbearing potential and men with partners of childbearing potential must
             be willing to use one highly effective form of non-hormonal contraception or two
             effective forms of non-hormonal contraception by the patient and/or partner and
             continue its use for the duration of the study treatment and for 7 months after the
             last dose of study treatment.

          -  Patients with a history of ipsilateral or contralateral DCIS or LCIS are eligible.

          -  Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any
             contraindications to radiation therapy.

          -  Non-English-speaking patients are eligible but will be exempt from patient-completed
             questionnaires.

          -  Willing and able to sign informed consent.

          -  Willing to undergo breast biopsy for research purposes.

        Exclusion Criteria:

          -  Pregnant or nursing women due to the teratogenic potential of the study drugs.

          -  Active, unresolved infection requiring intervention

          -  Receipt of intravenous antibiotics for infection within 7 days prior to registration.

          -  Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or
             clinically significant (i.e. active) cardiovascular disease: cerebrovascular
             accident/stroke or myocardial infarction within 6 months prior to first study
             medication, unstable angina, congestive heart failure (CHF) of New York Heart
             Association (NYHA) Class II or higher, or serious cardiac arrhythmia requiring
             medication.

          -  Significant symptoms (Grade ≥ 2) from peripheral neuropathy.

          -  Other concurrent serious diseases that may interfere with planned treatment, including
             severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.

          -  Any prior treatment for the current breast cancer, including chemotherapy, hormonal
             therapy, radiation, or experimental therapy.

          -  Patients with any prior history of invasive breast cancer within the past 5 years are
             not eligible. Non-metastatic invasive breast cancers diagnosed more than 5 years ago
             and any other type of prior non-metastatic cancer is allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of pathologic complete response (pCR)
Time Frame:12 weeks
Safety Issue:
Description:Compare rate of pathologic complete response (pCR, defined as RCB 0) in patients with the FF or FV CD16A genotype and anatomic stage II-III HER2+ breast cancer treated with 4 cycles of neoadjuvant TMP or THP

Secondary Outcome Measures

Measure:Rate of pathologic complete response
Time Frame:12 weeks
Safety Issue:
Description:Compare rate of pCR (RCB 0) in patients treated with TMP or THP, according to hormone receptor-positive (HR+) or hormone receptor-negative (HR-) status
Measure:Residual Cancer Burden (RCB) scores
Time Frame:12 weeks
Safety Issue:
Description:Assess Residual Cancer Burden (RCB) scores1 in patients treated with TMP or THP, overall and according to HR+ or HR- status. reported using the Residual Cancer Burden calculator from M.D Anderson:
Measure:Radiographic response rate
Time Frame:12 Weeks
Safety Issue:
Description:Assess radiographic response to neoadjuvant therapy in patients treated with TMP or THP, overall and according to HR+ or HR- status.Response criteria are based on the RECIST 1.1 criteria:
Measure:Number of Participants with Treatment Related Adverse Events according to CTCAE v5.0
Time Frame:From first treatment to 12 weeks
Safety Issue:
Description:Assessment of DLTs on Arm A during the first 21 days of treatment Maximum grade of all treatment-related adverse events according to CTCAE v5.0 Patient-reported outcomes
Measure:Event-free survival rate (EFS)
Time Frame:From enrollment to occurrence invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for EFS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Event-free survival rate (EFS) Patients with RCB 0 or 1
Time Frame:From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for EFS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Event-free survival rate (EFS)Patients with RCB 2 or 3
Time Frame:From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for EFS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Event-free survival rate (EFS) Patients randomized to neoadjuvant TMP
Time Frame:From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for EFS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Event-free survival rate (EFS) patients randomized to neoadjuvant THP
Time Frame:From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for EFS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Event-free survival rate (EFS) -Patients with pCR
Time Frame:From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for EFS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Event-free survival rate (EFS) -Patients without pCR
Time Frame:From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for EFS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Recurrence-free interval rate (RFI)
Time Frame:patients who undergo surgery for breast cancer as the interval from the time of surgery until the occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for RFI summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Recurrence-free interval rate (RFI) RCB 0 or 1
Time Frame:patients who undergo surgery for breast cancer as the interval from the time of surgery until the occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for RFI summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Recurrence-free interval rate (RFI) RCB 2 or 3
Time Frame:patients who undergo surgery for breast cancer as the interval from the time of surgery until the occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for RFI summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Recurrence-free interval rate (RFI) Patients randomized to neoadjuvant TMP
Time Frame:patients who undergo surgery for breast cancer as the interval from the time of surgery until the occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for RFI summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Recurrence-free interval rate (RFI) Patients randomized to neoadjuvant THP
Time Frame:patients who undergo surgery for breast cancer as the interval from the time of surgery until the occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for RFI summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Recurrence-free interval rate (RFI) Patients with pCR
Time Frame:patients who undergo surgery for breast cancer as the interval from the time of surgery until the occurrence of invasive local/regional recurrence distant recurrence ror death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for RFI summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Recurrence-free interval rate (RFI) Patients without pCR
Time Frame:patients who undergo surgery for breast cancer as the interval from the time of surgery until the occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for RFI summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Overall survival Rate (OS)
Time Frame:up to 10 years from definitive surgery.
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for OS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Overall survival Rate (OS) Patients with RCB 0 or 1
Time Frame:up to 10 years from definitive surgery.
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for OS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Overall survival Rate (OS) Patients with RCB 2 or 3
Time Frame:up to 10 years from definitive surgery.
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for OS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Overall survival Rate (OS) Patients randomized to neoadjuvant TMP
Time Frame:up to 10 years from definitive surgery.
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for OS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Overall survival Rate (OS) randomized to neoadjuvant THP
Time Frame:up to 10 years from definitive surgery.
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for OS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Overall survival Rate (OS) Patients with pCR
Time Frame:up to 10 years from definitive surgery.
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for OS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error
Measure:Overall survival Rate (OS) Patients without CR
Time Frame:up to 10 years from definitive surgery.
Safety Issue:
Description:The distribution of the survival function and cumulative incidence function for OS, summarized using the Kaplan Meier product limit estimator and 90% confidence interval (CI) using Greenwood's formula for the standard error

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Breast Cancer
  • Stage II Breast Cancer
  • Stage III Breast Cancer
  • HER2-positive Breast Cancer

Last Updated

June 8, 2020