Clinical Trials /

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

NCT04569747

Description:

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

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief 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
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 20-347
  • NCT ID: NCT04569747

Conditions

  • HER2-positive Breast Cancer
  • Invasive Carcinoma of the Breast
  • Breast Cancer
  • Node Negative Breast Cancer
  • Micrometastasis Breast Cancer
  • Hormone Receptor Positive Breast Cancer

Interventions

DrugSynonymsArms
ADJUVANT ENDOCRINE THERAPYLetrozole, Anastrozole, Exemestane, Tamoxifen, Leuprolide, or other LHRH agonist (per investigator discretion)PERTUZUMAB + TRASTUZUMAB + ADJUVANT ENDOCRINE THERAPY

Purpose

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

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.

      .
    

Trial Arms

NameTypeDescriptionInterventions
PERTUZUMAB + TRASTUZUMAB + ADJUVANT ENDOCRINE THERAPYExperimentalStudy 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)
  • ADJUVANT ENDOCRINE THERAPY

Eligibility Criteria

        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.

          -  ≤ 90 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.

          -  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.

          -  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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Invasive Disease Free Survival at 7 Years
Time Frame:7 years
Safety Issue:
Description: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
Measure:Invasive Disease Free Survival at 10 Years
Time Frame:10 years
Safety Issue:
Description: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
Measure:Recurrence-free interval (RFI) at 3 Years
Time Frame:3 Years
Safety Issue:
Description: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
Measure:Recurrence-free interval (RFI) at 7 Years
Time Frame:7 Years
Safety Issue:
Description: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
Measure:Recurrence-free interval (RFI) at 10 Years
Time Frame:10 Years
Safety Issue:
Description: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
Measure:Breast cancer-specific survival (BCSS) at 3 Years
Time Frame:3 Years
Safety Issue:
Description:defined as the time period between randomization and death due to breast cancer.
Measure:Breast cancer-specific survival (BCSS) at 7 Years
Time Frame:7 Years
Safety Issue:
Description:defined as the time period between randomization and death due to breast cancer.
Measure:Breast cancer-specific survival (BCSS) at 10 Years
Time Frame:10 Years
Safety Issue:
Description:defined as the time period between randomization and death due to breast cancer.
Measure: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
Safety Issue:
Description: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).
Measure:Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
Time Frame:baseline to 5 Years
Safety Issue:
Description:NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting

Details

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

Trial Keywords

  • HER2-positive Breast Cancer
  • Invasive Carcinoma of the Breast
  • Breast Cancer
  • Node Negative Breast Cancer
  • Micrometastasis Breast Cancer
  • Hormone Receptor Positive Breast Cancer

Last Updated

September 25, 2020