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

Breast Cancer Clinical Trial

— ADEPT  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04569747
• Other study ID #: 20-347
• Status: Recruiting
• Phase: Phase 2
• Start date: January 11, 2021
• Est. completion date: September 1, 2030

Study information

• Verified date: June 2024
• Source: Dana-Farber Cancer Institute
• Contact: Adrienne Waks, MD
• Phone: 617-632-3800
• Email: awaks[@]partners.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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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Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 375
• Est. completion date: September 1, 2030
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Combination Product:
• Pertuzumab+TRASTUZUMAB
Trastuzumab + pertuzumab SC FDC (PHESGO) will be administered on Day 1 of each 21-day cycle , subcutaneous, fixed dose

Drug:
• ADJUVANT ENDOCRINE THERAPY
Oral, daily per cycle

Locations

Country	Name	City	State
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	Winship Cancer Institute at Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Winship Cancer Institute at Emory University Hospital Midtown	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institite	Boston	Massachusetts
United States	Eastern Maine Medical Center (Northern Light)	Brewer	Maine
United States	New York University Langone Hospital -Brooklyn	Brooklyn	New York
United States	UNC Rex Hematology Oncology Associated - Cary	Cary	North Carolina
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Dana-Farber Brigham Cancer Center - Foxborough	Foxboro	Massachusetts
United States	UNC Rex Hematology Oncology Associates of Garner	Garner	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Cape Cod Healthcare Center	Hyannis	Massachusetts
United States	Indiana University Health - Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Indiana University Health Schwarz Cancer Center	Indianapolis	Indiana
United States	Indiana University Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana
United States	Dana-Farber Cancer Insitute at Londonderry Hospital	Londonderry	New Hampshire
United States	Dana-Farber at Milford	Milford	Massachusetts
United States	New York University Langone Hospital - Long Island	Mineola	New York
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	New York University Langone Health	New York	New York
United States	UNC Rex Cancer Center	Raleigh	North Carolina
United States	UNC Rex Cancer Center at Wakefield	Raleigh	North Carolina
United States	Stamford Hospital	Stamford	Connecticut
United States	Dana-Farber at South Shore Hospital	Weymouth	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient-reported hormonal therapy adherence	assessed by Voils questionnaire. Responses to survey items will be summarized using means or proportions depending on the nature of the questions.	5 years
Other	FACT B	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
Other	Rotterdam symptom checklist,	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
Other	WPAI-SHP-Work Productivity	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
Other	COST-Financial Toxicity	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
Other	Patient Acceptance of subcutaneous therapy (HPASQ-SC)	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
Other	Patient treatment experience time	Comparing FDC HP to IV HP in sub-study	baseline to 18 Months
Other	Patient drug administration time	Comparing FDC HP to IV HP in sub-study	baseline to 18 Months
Other	Pharmacist time commitment for drug preparation	Comparing FDC HP to IV HP in sub-study	baseline to 18 Months
Primary	Invasive Disease Free Survival at 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	Invasive Disease Free Survival at 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
Secondary	Invasive Disease Free Survival at 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
Secondary	Recurrence-free interval (RFI) at 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
Secondary	Recurrence-free interval (RFI) at 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
Secondary	Recurrence-free interval (RFI) at 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
Secondary	Breast cancer-specific survival (BCSS) at 3 Years	defined as the time period between randomization and death due to breast cancer.	3 Years
Secondary	Breast cancer-specific survival (BCSS) at 7 Years	defined as the time period between randomization and death due to breast cancer.	7 Years
Secondary	Breast cancer-specific survival (BCSS) at 10 Years	defined as the time period between randomization and death due to breast cancer.	10 Years
Secondary	Overall survival	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
Secondary	Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0	NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting	baseline to 5 Years
Secondary	Total patient chair time of drug administration	Mean difference will be estimated between HP FDC SC and IV admin of HP in sub-study	baseline to 18 Months