Breast CancerPhase 2MARGOTNCT04425018
MARGetuximab Or Trastuzumab (MARGOT)
A Phase 2 study testing Paclitaxel, Pertuzumab and Margetuximab in people with Breast Cancer and Stage II Breast Cancer, run by Dana-Farber Cancer Institute at 14 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer
- What is being tested?
- Paclitaxel, Pertuzumab and Margetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 174 participants
- Where
- 14 sitesUnited States
- Study dates
- 13 Jul 2020to 1 Jul 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 hasdetermined the patient should be treated as HER2-positive.
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- 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 treatment start. 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.
Who cannot join
- 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.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Dana-Farber Brigham Cancer Center - Foxborough
Foxborough, Massachusetts, 02035
UPMC Hillman Cancer Center - Arnold Palmer at Mountain View
Greensburg, Pennsylvania, 15601
Baylor College of Medicine Medical Center
Houston, Texas, 77030
MD Anderson Cancer Center
Houston, Texas, 77030
UPMC Hillman Cancer Center - Arnold Palmer at Norwin
Irwin, Pennsylvania, 15642
Dana-Farber at Milford
Milford, Massachusetts, 01757
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
University of Washington Fred Hutchinson Cancer Care
Seattle, Washington, 98109
Montefiore Medical Center
The Bronx, New York, 10461
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Dana-Farber at South Shore Hospital
Weymouth, Massachusetts, 02190
About this study
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
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 (Margenza)
- Paclitaxel, Pertzumab and Trastuzumab (Herceptin)
Read the 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 U.S. Food and Drug Administration (FDA) has approved margetuximab (Margenza) for advanced HER2-positive breast cancer.
- Conditions
- Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, HER2-positive Breast Cancer
- Being tested
- Paclitaxel, Pertuzumab, Margetuximab, Trastuzumab
- Keywords
- Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, HER2-positive Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxol, Onxal
Pre-determined dose administered via IV, Day 1,8,15 of each cycle 4 study cycles, or 12 weeks.
PertuzumabDrug
Also called Perjeta
Pre-determined dose administered via IV - Day 1 of each 21- day cycle 4 study cycles, or 12 weeks.
MargetuximabDrug
Also called Margenza
Pre-determined dose administered by IV - Day 1 of each 21- day cycle 4 study cycles, or 12 weeks.
TrastuzumabDrug
Also called Herceptin, Kanjinti, Ogivri, Herzuma
Pre-determined dose administered via IV Day 1 of each 21- day cycle for 4 study cycles, or 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Paclitaxel + Pertuzumab + Margetuximab | Experimental | The 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 Receives: Drug: Paclitaxel; Drug: Pertuzumab; Drug: Margetuximab |
| Paclitaxel + Pertuzumab + Trastuzumab | Experimental | The 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 Receives: Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response (pCR)
Compare the percentage of pathologic complete response (pCR) between patients treated with neoadjuvant TMP versus THP. Subject was considered a pCR responder if they achieved RCB 0 (no residual disease at surgery) and did not receive any additional non-protocol neoadjuvant treatment. Subject was considered a pCR non-responder if they did not achieve RCB 0 (RCB I, II, or III, or did not receive surgery) or if they received additional non-protocol neoadjuvant therapy.
RCB is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to 3, defined using established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB). Higher RCB score indicates more tumor burden remaining, thus worse outcome. RCB in this trial was determined according to local pathology review.
Measured: 12 weeks
Secondary outcomes (29)
Rate of Pathologic Complete Response in Hormone Receptor Positive (HR+) Subjects
In hormone receptor positive (HR+) patients, compare the rate of pathologic complete response (pCR) between patients treated with neoadjuvant TMP versus THP. Subject was considered a pCR responder if they achieved RCB 0 (no residual disease at surgery) and did not receive any additional non-protocol neoadjuvant treatment. Subject was considered a pCR non-responder if they did not achieve RCB 0 (RCB I, II, or III, or did not receive surgery) or if they received additional non-protocol neoadjuvant therapy.
RCB is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to 3, defined using established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB). Higher RCB score indicates more tumor burden remaining, thus worse outcome. RCB in this trial was determined according to local pathology review.
Measured: 12 weeks
Rate of Pathologic Complete Response in Hormone Receptor Negative (HR-) Subjects
In hormone receptor negative (HR-) patients, compare the rate of pathologic complete response (pCR) between patients treated with neoadjuvant TMP versus THP. Subject was considered a pCR responder if they achieved RCB 0 (no residual disease at surgery) and did not receive any additional non-protocol neoadjuvant treatment. Subject was considered a pCR non-responder if they did not achieve RCB 0 (RCB I, II, or III, or did not receive surgery) or if they received additional non-protocol neoadjuvant therapy.
RCB is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to 3, defined using established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB). Higher RCB score indicates more tumor burden remaining, thus worse outcome. RCB in this trial was determined according to local pathology review.
Measured: 12 weeks
Residual Cancer Burden (RCB) Scores
Assess Residual Cancer Burden (RCB) scores in patients treated with TMP or THP, reported using the Residual Cancer Burden calculator from M.D Anderson.
RCB is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to 3, defined using established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB). Higher RCB score indicates more tumor burden remaining, thus worse outcome. RCB in this trial was determined according to local pathology review.
Measured: 12 weeks
Residual Cancer Burden (RCB) Scores in Hormone Receptor Positive (HR+) Subjects
Among hormone receptor positive (HR+) patients, assess Residual Cancer Burden (RCB) scores in patients treated with TMP or THP, reported using the Residual Cancer Burden calculator from M.D Anderson.
Measured: 12 weeks
Residual Cancer Burden (RCB) Scores in Hormone Receptor Negative (HR-) Subjects
Among hormone receptor negative (HR-) subjects, assess Residual Cancer Burden (RCB) scores in patients treated with TMP or THP, reported using the Residual Cancer Burden calculator from M.D Anderson.
RCB is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to 3, defined using established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB). Higher RCB score indicates more tumor burden remaining, thus worse outcome. RCB in this trial was determined according to local pathology review.
Measured: 12 weeks
Dose-limiting Toxicities (DLTs) in theTMP Arm (Paclitaxel/Margetuximab/Pertuzumab) During the First 21 Days of Treatment
Among the subjects treated with TMP (Paclitaxel/Margetuximab/Pertuzumab), report the number of subjects with dose-limiting toxicities (DLTs) during the first 21 days of treatment, where 21 days equals one cycle of treatment. DLTs are defined in Section 5.4 of the protocol, with the specified toxicities and lab values categorized and graded according to CTCAE v5.0.
Measured: From first treatment to 21 days
Maximum Grade of All Treatment-related Adverse Events During Neoadjuvant Treatment
Maximum grade of all treatment-related adverse events (TRAEs) according to CTCAE v5.0 during neoadjuvant treatment, recorded per patient per arm. Subjects with no TRAEs reported (Grade 0) and Grade 1 adverse events are combined into a single category because only adverse events of Grade 2 or more were consistently reported.
Measured: Time from first dose of neoadjuvant treatment to start of de-escalated MP or HP protocol adjuvant therapy if subject received the de-escalated MP or HP protocol adjuvant therapy, up to 1 year after the last dose of their neoadjuvant treatment.
Patient-reported Outcomes
Patient-reported outcomes for symptoms and quality of life (both physical and mental health) during neoadjuvant TMP and THP
Measured: From first treatment to 12 weeks
Event-free Survival Rate (EFS)
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
Measured: From enrollment to occurrence invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Event-free Survival Rate (EFS) Patients With RCB 0 or 1
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
Measured: From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Event-free Survival Rate (EFS)Patients With RCB 2 or 3
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
Measured: From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Event-free Survival Rate (EFS) Patients Randomized to Neoadjuvant TMP
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
Measured: From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Event-free Survival Rate (EFS) Patients Randomized to Neoadjuvant THP
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
Measured: From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Event-free Survival Rate (EFS) -Patients With pCR
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
Measured: From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Event-free Survival Rate (EFS) -Patients Without pCR
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
Measured: From enrollment to occurrence of invasive local/regional recurrence distant recurrence or death from breast cancer or up to 10 years
Recurrence-free Interval Rate (RFI)
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
Measured: 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
Recurrence-free Interval Rate (RFI) RCB 0 or 1
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
Measured: 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
Recurrence-free Interval Rate (RFI) RCB 2 or 3
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
Measured: 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
Recurrence-free Interval Rate (RFI) Patients Randomized to Neoadjuvant TMP
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
Measured: 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
Recurrence-free Interval Rate (RFI) Patients Randomized to Neoadjuvant THP
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
Measured: 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
Recurrence-free Interval Rate (RFI) Patients With pCR
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
Measured: 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
Recurrence-free Interval Rate (RFI) Patients Without pCR
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
Measured: 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
Overall Survival Rate (OS)
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
Measured: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients With RCB 0 or 1
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
Measured: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients With RCB 2 or 3
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
Measured: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients Randomized to Neoadjuvant TMP
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
Measured: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Randomized to Neoadjuvant THP
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
Measured: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients With pCR
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
Measured: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients Without CR
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
Measured: up to 10 years from definitive surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start13 Jul 2020
- Primary completion24 Oct 2024
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- MacroGenics, Translational Breast Cancer Research Consortium
- Responsible party
- Principal investigator, Adrienne G. Waks, Dana-Farber Cancer Institute
- Investigators
- Adrienne Waks, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04425018
- Sponsor's protocol ID
- 20-068
- Acronym
- MARGOT
- Status last verified
- Nov 2025
- First submitted
- 15 Apr 2020
- Last updated
- 18 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04425018
- Acronym / sponsor ID
- MARGOT / 20-068
- Conditions
- Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, HER2-positive Breast Cancer
- Keywords
- Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer, HER2-positive Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 174 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- MacroGenics, Translational Breast Cancer Research Consortium
- Study start
- 13 Jul 2020 (actual)
- Primary completion
- 24 Oct 2024 (actual)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 22 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (Margenza)
- 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 U.S. Food and Drug Administration (FDA) has approved margetuximab (Margenza) for advanced HER2-positive breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paclitaxel + Pertuzumab + Margetuximab | Experimental | Drug: Paclitaxel, Drug: Pertuzumab, Drug: MargetuximabThe 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 + Trastuzumab | Experimental | Drug: Paclitaxel, Drug: Pertuzumab, Drug: TrastuzumabThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaclitaxelAlso: Taxol, OnxalPre-determined dose administered via IV, Day 1,8,15 of each cycle 4 study cycles, or 12 weeks. | Drug | Paclitaxel + Pertuzumab + Margetuximab, Paclitaxel + Pertuzumab + Trastuzumab |
| PertuzumabAlso: PerjetaPre-determined dose administered via IV - Day 1 of each 21- day cycle 4 study cycles, or 12 weeks. | Drug | Paclitaxel + Pertuzumab + Margetuximab, Paclitaxel + Pertuzumab + Trastuzumab |
| MargetuximabAlso: MargenzaPre-determined dose administered by IV - Day 1 of each 21- day cycle 4 study cycles, or 12 weeks. | Drug | Paclitaxel + Pertuzumab + Margetuximab |
| TrastuzumabAlso: Herceptin, Kanjinti, Ogivri, HerzumaPre-determined dose administered via IV Day 1 of each 21- day cycle for 4 study cycles, or 12 weeks. | Drug | Paclitaxel + Pertuzumab + Trastuzumab |
Primary outcome
Pathologic Complete Response (pCR)
Time frame: 12 weeks
Compare the percentage of pathologic complete response (pCR) between patients treated with neoadjuvant TMP versus THP. Subject was considered a pCR responder if they achieved RCB 0 (no residual disease at surgery) and did not receive any additional non-protocol neoadjuvant treatment. Subject was considered a pCR non-responder if they did not achieve RCB 0 (RCB I, II, or III, or did not receive surgery) or if they received additional non-protocol neoadjuvant therapy. RCB is used to assess the response to neoadjuvant chemotherapy in breast cancer patients and is in a scale of 0 to 3, defined using established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer_RCB). Higher RCB score indicates more tumor burden remaining, thus worse outcome. RCB in this trial was determined according to local pathology review.
29 secondary outcomes
Rate of Pathologic Complete Response in Hormone Receptor Positive (HR+) Subjects
Time frame: 12 weeks
Rate of Pathologic Complete Response in Hormone Receptor Negative (HR-) Subjects
Time frame: 12 weeks
Residual Cancer Burden (RCB) Scores
Time frame: 12 weeks
Residual Cancer Burden (RCB) Scores in Hormone Receptor Positive (HR+) Subjects
Time frame: 12 weeks
Residual Cancer Burden (RCB) Scores in Hormone Receptor Negative (HR-) Subjects
Time frame: 12 weeks
Dose-limiting Toxicities (DLTs) in theTMP Arm (Paclitaxel/Margetuximab/Pertuzumab) During the First 21 Days of Treatment
Time frame: From first treatment to 21 days
Maximum Grade of All Treatment-related Adverse Events During Neoadjuvant Treatment
Time frame: Time from first dose of neoadjuvant treatment to start of de-escalated MP or HP protocol adjuvant therapy if subject received the de-escalated MP or HP protocol adjuvant therapy, up to 1 year after the last dose of their neoadjuvant treatment.
Patient-reported Outcomes
Time frame: From first treatment to 12 weeks
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Overall Survival Rate (OS)
Time frame: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients With RCB 0 or 1
Time frame: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients With RCB 2 or 3
Time frame: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients Randomized to Neoadjuvant TMP
Time frame: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Randomized to Neoadjuvant THP
Time frame: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients With pCR
Time frame: up to 10 years from definitive surgery.
Overall Survival Rate (OS) Patients Without CR
Time frame: up to 10 years from definitive surgery.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrienne Waks, MD principal investigator
Dana-Farber Cancer Institute
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel, Pertuzumab and Margetuximab in people with Breast Cancer and Stage II Breast Cancer, run by Dana-Farber Cancer Institute at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Complete Response (pCR) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.