Clinical trial NCT05415215: A Study to Evaluate Patient Preference for Home Administration of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration in Participants With Early or Locally Advanced/Inflammatory HER2-Positive Breast Cancer
Official title: A Phase IIIB, Multinational, Multicenter, Randomized, Open-Label Study to Evaluate Patient Preference for Home Administration of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration in Participants With Early or Locally Advanced/Inflammatory HER2-Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Early Breast Cancer
Locally Advanced Breast Cancer
Inflammatory Breast Cancer
Keywords: patient preference
home administration
fixed-dose combination of pertuzumab and trastuzumab
subcutaneous administration
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-06-13
Enrollment: 347
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase IIIb, multinational, multicenter, randomized, open-label study to evaluate patient preference of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous use (PH FDC SC) administration in the home setting compared with the hospital setting during the cross-over period of adjuvant treatment in participants with early or locally advanced/inflammatory human epidermal growth factor receptor 2-positive (HER2+) breast cancer.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Intact skin at planned site of subcutaneous (SC) injections
* Left ventricular ejection fraction (LVEF) greater than or equal to (≥)55% by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
* Negative human immunodeficiency virus (HIV) test at screening
* Negative hepatitis B surface antigen (HBsAg) test at screening
* Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb); Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA test
* Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
* For female participants of childbearing potential: agreement to remain abstinent or use contraception and agree to refrain from donating eggs during the treatment period and for 7 months after the final dose of the study treatment
* For male participants: agreement to remain abstinent or use a condom, and agree to refrain from donating sperm during the treatment period and for 7 months after the final dose of study treatment

Disease-specific Inclusion Criteria:

* Female and male participants with stage II-IIIC early or locally advanced/inflammatory human epidermal growth factor receptor 2-positive (HER2+) breast cancer
* Primary tumor \>2 centimetres (cm) in diameter, or node-positive disease
* HER2+ breast cancer confirmed by a local laboratory prior to study enrollment. HER2+ status will be determined based on pretreatment breast biopsy material and defined as 3+ by Immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines 2018 and updates (Wolff et al. Arch Pathol Lab Med 2018)
* Hormone receptor status of the primary tumor determined by local assessment following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and updates (Allison et al. J Clin Oncol 2020)
* Agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy, including the axillary nodes
* Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for local confirmation of HER2 and hormone receptor status following current ASCO/CAP guidelines

Inclusion Criteria for Treatment with Adjuvant PH FDC SC:

* Completed the neoadjuvant phase of this study and underwent surgery, and achieved pathologic complete response (pCR), defined as eradication of invasive disease in the breast and axilla according to the current American Joint Committee on Cancer (AJCC) staging system classification, and using the resected specimen by the local pathologist on the basis of guidelines to be provided in a pathology manual
* Adequate wound healing after breast cancer surgery per investigator's assessment to allow initiation of study treatment within less than or equal to (≤)9 weeks of last systemic neoadjuvant therapy

Exclusion Criteria:

* Stage IV (metastatic) breast cancer
* History of concurrent or previously treated non-breast malignancies, except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin. A participant with previous invasive non-breast cancer is eligible provided he/she has been disease free for more than 5 years
* Participants who are pregnant or breastfeeding or intending to become pregnant during the study or within 7 months after the final dose of study treatments
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Active, unresolved infections at screening requiring treatment
* Participants who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their International Normalized Ratio (INR)
* Serious cardiac illness or medical conditions
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
* Inadequate bone marrow function
* Impaired liver function
* Renal function with creatinine clearance \<50 mL/min using the Cockroft-Gault formula and serum creatinine \>1.5x upper limit of normal (ULN)
* Major surgical procedure unrelated to breast cancer within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment
* Current severe, uncontrolled systemic disease that may interfere with planned treatment
* Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
* Treatment with a live vaccine (e.g., FluMist) in the 30 days prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment or within 90 days after the final dose of study treatment
* Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis
* Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins or a history of severe allergic or immunological reactions, e.g., difficult to control asthma
* Current chronic daily treatment with corticosteroids
* Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol

Cancer-specific Exclusion Criteria for Neoadjuvant Phase:

* Participants who have received any previous systemic therapy for treatment or prevention of breast cancer, or previous chest irradiation for the treatment of cancer
* Participants who have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsi- or contralateral breast cancer
* Participants with high-risk for breast cancer who have received chemopreventive drugs in the past
* Participants with multicentric breast cancer, unless all tumors are HER2+
* Participants with bilateral breast cancer
* Participants who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes
* Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy
* Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy

Exclusion Criterion for Treatment with Adjuvant Trastuzumab Emtansine (Arm E):

* Current Grade ≥3 peripheral neuropathy (according to the NCI CTCAE v5.0)

Primary outcomes:
measure: Percentage of Participants Who Preferred the Administration of PH FDC SC in the Home Setting Compared With the Hospital Setting, Question 1 of the Patient Preference Questionnaire
timeFrame: Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary outcomes:
measure: Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Neoadjuvant Phase Drug Preparation Area
timeFrame: Day 1 of each cycle from first cycle (Cycle 1 or 5) to last cycle (Cycle 6 or 8) of PH IV or PH FDC SC neoadjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Neoadjuvant Phase Drug Preparation Area
timeFrame: Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Neoadjuvant Phase Drug Preparation Area
timeFrame: Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
measure: Duration of Treatment Administration Activities, According to Healthcare Professionals' Responses to Question 1 of the HCPQ - Neoadjuvant Phase Administering Treatment
timeFrame: Day 1 of each cycle from first cycle (Cycle 1 or 5) to last cycle (Cycle 6 or 8) of PH IV or PH FDC SC neoadjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Neoadjuvant Phase Administering Treatment
timeFrame: Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 10 of the HCPQ - Neoadjuvant Phase Administering Treatment
timeFrame: Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses to Question 11 of the HCPQ - Neoadjuvant Phase Administering Treatment
timeFrame: Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Participants Achieving Pathologic Complete Response (pCR)
timeFrame: Post-surgery (up to 27 weeks)
measure: Health-Related Quality of Life Assessed by the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ)-C30 Questionnaire Scores in the Neoadjuvant Phase
timeFrame: Day 1 of Cycle 1 and Day 1 of last cycle of neoadjuvant treatment (Cycle 6 or 8; 1 cycle is 3 weeks)
measure: Health-Related Quality of Life Assessed by the EORTC QLQ-C30 Questionnaire Scores in Participants Treated with PH FDC SC During the Adjuvant Phase
timeFrame: Day 1 of Cycles 1, 3, 5, 8, and last cycle of adjuvant treatment (1 cycle is 3 weeks)
measure: Health-Related Quality of Life Assessed by the EORTC QLQ-C30 Questionnaire Scores in Participants Treated with Trastuzumab Emtansine During the Adjuvant Phase
timeFrame: Day 1 of Cycles 1, 7, and 14 of adjuvant treatment (1 cycle is 3 weeks)
measure: Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1 of the HCPQ - Adjuvant Phase Drug Preparation Area
timeFrame: Day 1 of Cycles 5 and 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of the Treatment Setting's Impact on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Adjuvant Phase Drug Preparation Area
timeFrame: Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of Time/Resource Use in the Home and Hospital Settings, Questions 3 and 4 of the HCPQ - Adjuvant Phase Drug Preparation Area
timeFrame: Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Duration of Treatment Administration Activities, According to Healthcare Professionals' Responses to Question 1 of the HCPQ - Adjuvant Phase Administering Treatment
timeFrame: Day 1 of Cycles 5 and 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of the Treatment Setting's Impact on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Adjuvant Phase Administering Treatment
timeFrame: Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses on Perception of Time/Resource Use in the Home and Hospital Settings, Questions 3 to 6 of the HCPQ - Adjuvant Phase Administering Treatment
timeFrame: Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Healthcare Professionals by Their Responses to Question 7 of the HCPQ - Adjuvant Phase Administering Treatment
timeFrame: Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Percentage of Participants who Selected the Administration of PH FDC SC in the Home Setting Compared With the Hospital Setting in the Treatment Continuation Period
timeFrame: Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
measure: Number of Participants with at Least One Adverse Event During the Neoadjuvant Treatment Phase, with Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)
timeFrame: From Baseline until surgery (up to 27 weeks)
measure: Incidence of Premature Withdrawal from Neoadjuvant Treatment with PH FDC SC or Pertuzumab IV and Trastuzumab IV
timeFrame: From Cycle 1 to last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
measure: Number of Participants with Clinical Laboratory Test Abnormalities During the Neoadjuvant Treatment Phase
timeFrame: From Baseline until surgery (up to 27 weeks)
measure: Number of Participants with Vital Sign Abnormalities During the Neoadjuvant Treatment Phase
timeFrame: From Baseline until surgery (up to 27 weeks)
measure: Number of Participants with at Least One Adverse Event During the Adjuvant Treatment Phase, with Severity Determined According to the NCI CTCAE v5.0
timeFrame: From first dose post-surgery up to 9 months after the last dose of adjuvant treatment (up to 2 years)
measure: Incidence of Premature Withdrawal from Adjuvant Treatment with PH FDC SC
timeFrame: From Cycle 1 to last cycle (Cycle 12 or 14) of adjuvant treatment (1 cycle is 3 weeks)
measure: Incidence of Premature Withdrawal from Adjuvant Treatment with Trastuzumab Emtansine
timeFrame: From Cycle 1 to Cycle 14 (last cycle; 1 cycle is 3 weeks)
measure: Number of Participants with Clinical Laboratory Test Abnormalities During the Adjuvant Treatment Phase
timeFrame: From first dose post-surgery until the last dose of adjuvant treatment (up to 1.5 years)
measure: Number of Participants with Vital Sign Abnormalities During the Adjuvant Treatment Phase
timeFrame: From first dose post-surgery until the last dose of adjuvant treatment (up to 1.5 years)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro Oncologico Korben
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of the Republic of Srpska
city: Zenica
country: Bosnia and Herzegovina
facility: Cantonal Hospital Zenica
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: Ceará
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge
state: Goiás
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
state: São Paulo
city: Panagyurishte
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Uni Hospital
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv First Internal Chemotherapy Department
city: Sofia
country: Bulgaria
facility: MHAT Nadezhda
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Hopital du Saint Sacrement
state: Quebec
city: Santiago
country: Chile
facility: Clinica Vespucio
city: Santiago
country: Chile
facility: Centro de Estudios Clínicos SAGA
city: San Jose
country: Costa Rica
facility: Hospital Metropolitano (Sede Lindora-Santa Ana)
city: San José
country: Costa Rica
facility: Clinica CIMCA
city: San José
country: Costa Rica
facility: ICIMED Instituto de Investigación en Ciencias Médicas
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Mumbai
country: India
facility: Saifee Hospital
state: Maharashtra
city: Kolkata
country: India
facility: TATA Medical Centre
state: WEST Bengal
city: Eldoret
country: Kenya
facility: International Cancer Institute (ICI)
city: Nairobi
country: Kenya
facility: Aga Khan University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY
city: D.f.
country: Mexico
facility: Iem-Fucam
state: Mexico CITY
city: San Luis Potosí
country: Mexico
facility: Oncologico Potosino
state: SAN LUIS Potosi
city: Arequipa
country: Peru
facility: Instituto Regional de Enfermedades Neoplásicas del Sur
city: Lima
country: Peru
facility: Oncocenter Peru S.A.C.
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
city: Pretoria
country: South Africa
facility: Wilgers Oncology Centre
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de Arrixaca
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Ankara
country: Turkey
facility: Gulhane Training and Research Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
city: Istanbul
country: Turkey
facility: Ba?c?lar Medipol Mega Üniversite Hastanesi
city: Sihhiye/Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: