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)
T
Tarah Ballinger, MD
Primary Investigator
Overview
This research study is studying a combination of HER2-directed therapies (trastuzumab anduzumab) 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
Description
The research study procedures include screening for eligibility and study treatment includingboratory evaluations, physical exams, questionnaires, and follow up visits.
- Participants will receive HER2-directed treatment for 1 year and hormonal therapy fory 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 safetyd effectiveness of an investigational drug combination to learn whether the drug works ing a specific disease. "Investigational" means that the drug combination is beingudied.
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 alsoved hormonal therapies as treatment for hormone receptor positive breast cancer.
.
Eligibility
You may be eligible for this study if you meet the following criteria:
-
Conditions:
HER2-positive Breast Cancer, Invasive Carcinoma of the Breast, Breast Cancer, Node Negative Breast Cancer, Micrometastasis Breast Cancer, Hormone Receptor Positive Breast Cancer
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Age: 18 Years
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Gender: All
Inclusion Criteria:
- HER2-positive T1 histologically confirmed invasive carcinoma of the breast. Patientsust have node-negative (N0) or micrometastases (N1mi) breast cancer according to theAJCC 8th edition anatomic staging table.
- If the patient has had a negative sentinel node biopsy, then no further axillarydissection 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 orunohistochemistry (IHC) will be considered node-negative.
- Any axillary lymph node with tumor clusters between 0.02 and 0.2cm is considered. Patients with a micrometastasis are eligible. An axillarydissection is not required to be performed in patients with a micrometastasisund by sentinel node evaluation. In cases where the specific pathologic size ofymph node involvement is subject to interpretation, the overall principalvestigator will make the final determination as to eligibility. Thevestigator must document approval in the patient medical record.
- Patients who have an area of T1aN0, ER+ (defined as ≥ 10%), HER2-negative cancerher 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%PR ≥10%. ER- and PR-assays should be performed by immunohistochemical methodsding to the local institution standard protocol.
- HER2-positive by ASCO CAP 2018 guidelines, confirmed by central testing. See AppendixASCO 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 tog protocol therapy. Patients previously having had HER2 testing byGenomics do not need to undergo retesting for central confirmation of HER2us. A pathology report documenting testing by NeoGenomics should be providedgistration.
- Bilateral breast cancers that individually meet eligibility criteria are allowed.
- Patients with multifocal or multicentric disease are eligible as long as each tumordividually meets eligibility criteria, with the following exceptions: (1) centralHER2 status is needed only for any site of disease that is tested tobe 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 (asdefined above).
- Patients with a history of ipsilateral DCIS are eligible as long as the patient hasved prior hormonal therapy. Patients with a history of contralateral DCIS aregible unless contralateral DCIS was diagnosed at least 15 years ago
- ≤ 95 days between the date of protocol registration and the patient's most recentbreast surgery for this breast cancer
- Patients must have undergone definitive breast surgery for the current malignancy. Allumor should be removed by either a modified radical mastectomy or a segmentaly (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). Thehologist must document negative margins of resection in the pathology report.her margins are clear, a positive posterior (deep) margin is permitted,vided the surgeon documents that the excision was performed down to the pectorald all tumor has been removed. Likewise, if all other margins are clear, ave anterior (superficial; abutting skin) margin is permitted provided theurgeon documents that all tumor has been removed. Radiation therapy to the conservedbreast is required.
- May have received up to 8 weeks of hormonal therapy as adjuvant treatment for this. Patients should otherwise not have received prior hormonal therapy with thehat hormonal therapy administered for less than 8-week duration at least 15years ago is allowed.
- Prior oophorectomy (including for cancer therapy) is allowed.
- Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have anydications to radiation therapy.
- Patients who have participated in a window study (treatment with an investigationalgent prior to surgery for ≤2 weeks) are eligible. Patients must have discontinued thevestigational 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 directbilirubin 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 monthshemotherapy and/or endocrine therapy exposure (medication-inducedhea is not acceptable to meet this criterion)
- Age < 60 years hysterectomized and FSH and plasma estradiol levels in theusal range according to local policies prior to chemotherapy and/ordocrine 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 urinegnancy test, including women who have had a tubal ligation and women less than 12hs from their last menstrual period.
- Women of childbearing potential and men with partners of childbearing potential mustbe willing to use one highly effective form of nonhormonal contraception or twove forms of nonhormonal contraception by the patient and/or partner andue its use for the duration of the study treatment and for 7 months after thedose of antibody treatment and 3 months after the last dose of hormonal.
- 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 ishibited.
- 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(condoms, diaphragms, IUDS, surgical sterilization, abstinence,). Hormonal birth control methods are not permitted.
- Men who are unwilling to employ adequate contraception (condoms, surgicalzation, 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, peaud'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawnyutaneous 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 thewing circumstances:
- Individuals with a history of other malignancies are eligible if they have beendisease-free for at least 5 years and are deemed by the investigator to be at lowk for recurrence of that malignancy.
- individuals with the following cancer are eligible regardless of when they werediagnosed and treated: cervical cancer in situ, and non-melanoma cancer of thekin.
- Intercurrent illness including, but not limited to: ongoing or active, unresolved
systemic infection, renal failure requiring dialysis, active cardiac disease, prioryocardial infarction (asymptomatic changes on EKG suggestive of old MI is not anusion), history of CHF, current use of any therapy specifically for CHF,uncontrolled hypertension, significant psychiatric illness, or other conditions thathe 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
Updated on
08 May 2024.
Study ID: 20-347
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