A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer (ADEPT)

November 16, 2023 updated by: Adrienne G. Waks, Dana-Farber Cancer Institute

20-347 NCT Number Title A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer (ADEPT)

This research study is studying a combination of HER2-directed therapies (trastuzumab and pertuzumab) and hormonal therapy as a treatment after surgery for hormone receptor positive breast cancer.

The study drugs involved in this study are:

  • A combination of trastuzumab and pertuzumab given as an injection under the skin (PHESGO)
  • Hormonal (endocrine) Treatment

Study Overview

Detailed Description

The research study procedures include screening for eligibility and study treatment including laboratory evaluations, physical exams, questionnaires, and follow up visits.

  • Participants will receive HER2-directed treatment for 1 year and hormonal therapy for approximately 5 years.
  • It is expected that about 375 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 works in treating a specific disease. "Investigational" means that the drug combination is being studied.

The drugs trastuzumab and pertuzumab are both monoclonal antibodies, which are disease-fighting proteins made by cloned immune cells. The U.S. Food and Drug Administration (FDA) has approved trastuzumab, pertuzumab, and trastuzumab + pertuzumab subcutaneous fixed dose combination (PHESGO) as treatment for HER2 positive breast cancer. The FDA has also approved hormonal therapies as treatment for hormone receptor positive breast cancer.

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Study Type

Interventional

Enrollment (Estimated)

375

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Connecticut
      • Stamford, Connecticut, United States, 06904
        • Recruiting
        • Stamford Hospital
        • Contact:
        • Principal Investigator:
          • K. M. Steve Lo, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University - Winship Cancer Institute
        • Principal Investigator:
          • Jane Meisel, MD
        • Contact:
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Winship Cancer Institute at Emory University Hospital Midtown
        • Contact:
        • Principal Investigator:
          • Jane Meisel, MD
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Winship Cancer Institute at Emory Saint Joseph's Hospital
        • Contact:
        • Principal Investigator:
          • Jane Meisel, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46032
        • Recruiting
        • Indiana University Health Schwarz Cancer Center
        • Contact:
        • Principal Investigator:
          • Tarah Ballinger, MD
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University Health - Melvin and Bren Simon Cancer Center
        • Contact:
        • Principal Investigator:
          • Tarah J Ballinger, MD
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University Sidney and Lois Eskenazi Hospital
        • Contact:
        • Principal Investigator:
          • Tarah Ballinger, MD
    • Maine
      • Brewer, Maine, United States, 04412
        • Recruiting
        • Eastern Maine Medical Center (Northern Light)
        • Contact:
        • Principal Investigator:
          • Sarah J Sinclair, DO
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Beth Israel Deaconess Medical Center
        • Contact:
        • Principal Investigator:
          • Nadine Tung, MD
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Dana Farber Cancer Institite
        • Contact:
        • Principal Investigator:
          • Adrienne Waks, MD
      • Foxboro, Massachusetts, United States, 02035
        • Recruiting
        • Dana-Farber Brigham Cancer Center - Foxborough
        • Principal Investigator:
          • Natalie Sinclair, MD
        • Contact:
      • Milford, Massachusetts, United States, 01757
        • Recruiting
        • Dana-Farber at Milford
        • Principal Investigator:
          • Natalie Sinclair, MD
        • Contact:
      • Weymouth, Massachusetts, United States, 02190
        • Recruiting
        • Dana-Farber at South Shore Hospital
        • Principal Investigator:
          • Meredith Faggen, MD
        • Contact:
    • New Hampshire
      • Londonderry, New Hampshire, United States, 03053
        • Recruiting
        • Dana-Farber Cancer Insitute at Londonderry Hospital
        • Contact:
        • Principal Investigator:
          • Jeanna Walsh, MD
    • New York
      • Mineola, New York, United States, 11501
      • New York, New York, United States, 10016
    • North Carolina
      • Cary, North Carolina, United States, 27518
        • Recruiting
        • UNC Rex Hematology Oncology Associated - Cary
        • Contact:
        • Principal Investigator:
          • Julia Rauch, MD
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina at Chapel Hill
        • Principal Investigator:
          • Lisa Carey, MD
        • Contact:
      • Garner, North Carolina, United States, 27529
        • Recruiting
        • UNC Rex Hematology Oncology Associates of Garner
        • Contact:
        • Principal Investigator:
          • Julia Rauch, MD
      • Raleigh, North Carolina, United States, 27607
      • Raleigh, North Carolina, United States, 27614
        • Recruiting
        • UNC Rex Cancer Center at Wakefield
        • Contact:
        • Principal Investigator:
          • Julia Rauch, MD
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Nicole Williams, MD
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute
        • Contact:
        • Principal Investigator:
          • Denise Yardley, MD
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Vanderbilt University Medical Center
        • Principal Investigator:
          • Vandana Abramson, MD
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Vicente Valero, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • HER2-positive T1 histologically confirmed invasive carcinoma of the breast. Patients must have node-negative (N0) or micrometastases (N1mi) breast cancer according to the AJCC 8th edition anatomic staging table.

    • If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative. Axillary nodes with single cells or tumor clusters ≤ 0.2 mm by either H&E or immunohistochemistry (IHC) will be considered node-negative.
    • Any axillary lymph node with tumor clusters between 0.02 and 0.2cm is considered a micrometastasis. Patients with a micrometastasis are eligible. An axillary dissection is not required to be performed in patients with a micrometastasis found by sentinel node evaluation. In cases where the specific pathologic size of lymph node involvement is subject to interpretation, the overall principal investigator will make the final determination as to eligibility. The investigator must document approval in the patient medical record.
    • Patients who have an area of T1aN0, ER+ (defined as ≥ 10%), HER2-negative cancer in either breast, in addition to their primary HER2 positive tumor, are eligible.
  • For unifocal disease, all invasive disease must have been tested for ER and PR (for multifocal disease, see below). Either ER or PR must be positive, defined as ER ≥10% or PR ≥10%. ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol.
  • HER2-positive by ASCO CAP 2018 guidelines, confirmed by central testing. See Appendix I for ASCO CAP 2018 HER2 testing guidelines.

    • NOTE: DCIS components will not be counted in the determination of HER2 status
    • NOTE: HER-2 status must be confirmed to be positive by central review prior to patient starting protocol therapy. Patients previously having had HER2 testing by NeoGenomics do not need to undergo retesting for central confirmation of HER2 status. A pathology report documenting testing by NeoGenomics should be provided at time of patient registration.
  • Bilateral breast cancers that individually meet eligibility criteria are allowed.
  • Patients with multifocal or multicentric disease are eligible as long as each tumor individually meets eligibility criteria, with the following exceptions: (1) central confirmation of HER2 status is needed only for any site of disease that is tested to be HER2-positive by local testing (unless original testing was done by NeoGenomics); (2) all areas that were locally tested for ER and PR status must be ER/PR positive (as defined above).
  • Patients with a history of ipsilateral DCIS are eligible as long as the patient has not received prior hormonal therapy. Patients with a history of contralateral DCIS are not eligible unless contralateral DCIS was diagnosed at least 15 years ago
  • ≤ 95 days between the date of protocol registration and the patient's most recent breast surgery for this breast cancer
  • Patients must have undergone definitive breast surgery for the current malignancy. All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy), with either a sentinel node biopsy or axillary dissection

    -- All margins should be clear of invasive cancer or DCIS (i.e. no tumor on ink). The local pathologist must document negative margins of resection in the pathology report. If all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed. Likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed. Radiation therapy to the conserved breast is required.

  • May have received up to 8 weeks of hormonal therapy as adjuvant treatment for this cancer. Patients should otherwise not have received prior hormonal therapy with the exception that hormonal therapy administered for less than 8-week duration at least 15 years ago is allowed.
  • Prior oophorectomy (including for cancer therapy) is allowed.
  • Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy.
  • Patients who have participated in a window study (treatment with an investigational agent prior to surgery for ≤2 weeks) are eligible. Patients must have discontinued the investigational agent at least 14 days before participation in this study.
  • Men and women with any menopausal status ≥18 years of age
  • ECOG Performance Status 0 or 1
  • Participants must have normal organ and marrow function as defined below:

    • ANC ≥ 1000/mm3
    • hemoglobin ≥8 g/dl
    • platelets ≥ 75,000/mm3
    • AST and ALT both <5x institutional ULN
    • Total bilirubin ≤ 1.5 mg/dL. For patients with Gilbert syndrome, the direct bilirubin should be <institutional ULN
    • Serum creatinine ≤ 2.0 mg/dL OR calculated GFR ≥ 30mL/min
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • Post-menopausal patients must meet one of the following criteria:

    • Prior bilateral ovariectomy/oophorectomy
    • Age ≥ 60 years
    • Age < 60 years with intact uterus and amenorrhoeic for ≥ 12 consecutive months prior to chemotherapy and/or endocrine therapy exposure (medication-induced amenorrhea is not acceptable to meet this criterion)
    • Age < 60 years hysterectomized and FSH and plasma estradiol levels in the postmenopausal range according to local policies prior to chemotherapy and/or endocrine therapy exposure.
  • Willingness to discontinue contraceptive hormonal therapy, e.g. birth control pills, prior to registration and while on study
  • Premenopausal patients with intact uterus must have a negative serum or urine pregnancy test, including women who have had a tubal ligation and women less than 12 months from their last menstrual period.
  • Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of nonhormonal contraception or two effective forms of nonhormonal 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 antibody treatment and 3 months after the last dose of hormonal treatment.
  • Patients must be willing and able to sign informed consent.
  • Patients must be willing to provide archival tissue for research purposes.
  • If patient is English-speaking, must be willing to fill out patient questionnaires.

Exclusion Criteria:

  • Neoadjuvant or adjuvant chemotherapy for this breast cancer prior to enrollment is prohibited.
  • Any of the following due to teratogenic potential of the study drugs:

    • Pregnant women
    • Nursing women
    • Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence, etc). Hormonal birth control methods are not permitted.
    • Men who are unwilling to employ adequate contraception (condoms, surgical sterilization, abstinence, etc).
  • Participants who are receiving any other investigational agents for treatment of breast cancer, unless specific approval is obtained from the Sponsor-Investigator.
  • Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
  • Patients with a history of previous invasive breast cancer.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances:

    • Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy.
    • individuals with the following cancer are eligible regardless of when they were diagnosed and treated: cervical cancer in situ, and non-melanoma cancer of the skin.
  • Intercurrent illness including, but not limited to: ongoing or active, unresolved systemic infection, renal failure requiring dialysis, active cardiac disease, prior myocardial infarction (asymptomatic changes on EKG suggestive of old MI is not an exclusion), history of CHF, current use of any therapy specifically for CHF, uncontrolled hypertension, significant psychiatric illness, or other conditions that in the opinion of the investigator limit compliance with study requirements.

Time and Motion Substudy Eligibility:

  • Participant must be enrolled at Dana-Farber Cancer Institute
  • Participant must not have discontinued pertuzumab following treatment cycle 1
  • Participant must be able to tolerate subcutaneous administration following cycle 1

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PERTUZUMAB + TRASTUZUMAB + ADJUVANT ENDOCRINE THERAPY

Study treatment will be administered in 21-day (3- week, +/- 3 days) cycles for one year (18 cycles).

  • Trastuzumab + Pertuzumab SC fixed dose combination
  • Hormonal therapy- oral, daily per cycle (may add LHRH agonist per investigator discretion)
Trastuzumab + pertuzumab SC FDC (PHESGO) will be administered on Day 1 of each 21-day cycle , subcutaneous, fixed dose
Other Names:
  • PHESGO
Oral, daily per cycle
Other Names:
  • Exemestane
  • Letrozole
  • Anastrozole
  • Tamoxifen
  • Leuprolide, or other LHRH agonist (per investigator discretion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Invasive Disease Free Survival at 3 Years
Time Frame: 3 Years

Kaplan-Meier estimates of iDFS will be estimated and plotted with the corresponding 95% confidence intervals.

from the time of randomization until the occurrence of the first of the following events: invasive local/regional recurrence, Contralateral invasive breast cancer, Distant recurrence, Death from any cause

3 Years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Invasive Disease Free Survival at 7 Years
Time Frame: 7 years

Kaplan-Meier estimates of iDFS will be estimated and plotted with the corresponding 95% confidence intervals.

from the time of randomization until the occurrence of the first of the following events: invasive local/regional recurrence, Contralateral invasive breast cancer, Distant recurrence, Death from any cause

7 years
Invasive Disease Free Survival at 10 Years
Time Frame: 10 years

Kaplan-Meier estimates of iDFS will be estimated and plotted with the corresponding 95% confidence intervals.

from the time of randomization until the occurrence of the first of the following events: invasive local/regional recurrence, Contralateral invasive breast cancer, Distant recurrence, Death from any cause

10 years
Recurrence-free interval (RFI) at 3 Years
Time Frame: 3 Years
RFI will be estimated and plotted with the corresponding 95% confidence intervals, using Kaplan-Meier estimates for the study as a whole and for subgroups of patients determined by intrinsic subtype (HER2-enriched, luminal, basal Time of randomization until the occurrence of the first of the following events:Invasive local/regional recurrence, Distant recurrence, Death from breast cancer
3 Years
Recurrence-free interval (RFI) at 7 Years
Time Frame: 7 Years
RFI will be estimated and plotted with the corresponding 95% confidence intervals, using Kaplan-Meier estimates for the study as a whole and for subgroups of patients determined by intrinsic subtype (HER2-enriched, luminal, basal Time of randomization until the occurrence of the first of the following events:Invasive local/regional recurrence, Distant recurrence, Death from breast cancer
7 Years
Recurrence-free interval (RFI) at 10 Years
Time Frame: 10 Years
RFI will be estimated and plotted with the corresponding 95% confidence intervals, using Kaplan-Meier estimates for the study as a whole and for subgroups of patients determined by intrinsic subtype (HER2-enriched, luminal, basal Time of randomization until the occurrence of the first of the following events:Invasive local/regional recurrence, Distant recurrence, Death from breast cancer
10 Years
Breast cancer-specific survival (BCSS) at 3 Years
Time Frame: 3 Years
defined as the time period between randomization and death due to breast cancer.
3 Years
Breast cancer-specific survival (BCSS) at 7 Years
Time Frame: 7 Years
defined as the time period between randomization and death due to breast cancer.
7 Years
Breast cancer-specific survival (BCSS) at 10 Years
Time Frame: 10 Years
defined as the time period between randomization and death due to breast cancer.
10 Years
Overall survival
Time Frame: randomization and death. Surviving patients classified as lost-to-follow-up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first up to 10 years
OS will be estimated and plotted with the corresponding 95% confidence intervals, using Kaplan-Meier estimates for the study as a whole and for subgroups of patients determined by intrinsic subtype (HER2-enriched, luminal, basal).
randomization and death. Surviving patients classified as lost-to-follow-up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first up to 10 years
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Time Frame: baseline to 5 Years
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting
baseline to 5 Years
Total patient chair time of drug administration
Time Frame: baseline to 18 Months
Mean difference will be estimated between HP FDC SC and IV admin of HP in sub-study
baseline to 18 Months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient-reported hormonal therapy adherence
Time Frame: 5 years
assessed by Voils questionnaire. Responses to survey items will be summarized using means or proportions depending on the nature of the questions.
5 years
FACT B
Time Frame: baseline to 18 Months
The FACT-B includes the FACT-G, a 27-item generic cancer questionnaire and a 10- item breast cancer specific module. Responses to survey items will be summarized by means or proportions depending on the nature of the items
baseline to 18 Months
Rotterdam symptom checklist,
Time Frame: baseline to 18 Months

The Activity Level Scale Domain from the RSCL is an 8-item scale designed to measure whether the respondent can perform a series of activities at the present time. Items are summed to produce an overall score, with higher scores representing better functioning.

Responses to survey items will be summarized by means or proportions

baseline to 18 Months
WPAI-SHP-Work Productivity
Time Frame: baseline to 18 Months
The WPAI was created as a patient-reported quantitative assessment of the amount of absenteeism, presenteeism and daily activity impairment attributable to general health (WPAI:GH) or a specific health problem (WPAI:SHP). The 6 questions in the WPAI questionnaire were generated from three main sources Responses to survey items will be summarized by means or proportions depending on the nature of the items
baseline to 18 Months
COST-Financial Toxicity
Time Frame: baseline to 18 Months
There is increasing recognition of the profound importance of the financial strain on patients created by cancer diagnosis and therapies. The COST (Comprehensive Score for financial Toxicity) measure has been developed and validated as a mechanism to assess financial stress related to cancer diagnosis and treatment Responses to survey items will be summarized by means or proportions
baseline to 18 Months
Patient Acceptance of subcutaneous therapy (HPASQ-SC)
Time Frame: baseline to 18 Months

The HPASQ-SC (Appendix C) is a tool to measure patient-reported outcomes regarding patient acceptance of subcutaneous therapy. It was developed and underwent validity testing in a cohort of patients receiving subcutaneous rituximab for lymphoma. The HPASQ-SC contains questions related to two main concepts (treatment satisfaction and impact of treatment administration) and eight sub-concepts: overall preference/satisfaction; convenience; confidence; bothersome-ness; physical impact; psychological impact; impact on activities of daily life; and impact on the interaction with healthcare providers.21

Responses to survey items will be summarized by means or proportions

baseline to 18 Months
Patient treatment experience time
Time Frame: baseline to 18 Months
Comparing FDC HP to IV HP in sub-study
baseline to 18 Months
Patient drug administration time
Time Frame: baseline to 18 Months
Comparing FDC HP to IV HP in sub-study
baseline to 18 Months
Pharmacist time commitment for drug preparation
Time Frame: baseline to 18 Months
Comparing FDC HP to IV HP in sub-study
baseline to 18 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Adrienne C Waks, MD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 11, 2021

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2030

Study Registration Dates

First Submitted

September 25, 2020

First Submitted That Met QC Criteria

September 25, 2020

First Posted (Actual)

September 30, 2020

Study Record Updates

Last Update Posted (Estimated)

November 20, 2023

Last Update Submitted That Met QC Criteria

November 16, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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 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.

IPD Sharing Time Frame

Data can be shared no earlier than 1 year following the date of publication

IPD Sharing Access Criteria

DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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