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

Locally Advanced Breast Cancer Clinical Trial

— ProHer  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05415215
• Other study ID #: MO43110
• Secondary ID: 2021-002346-3320
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 5, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 347
• Est. completion date: December 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Breast Neoplasms
• Early Breast Cancer
• Inflammatory Breast Cancer
• Locally Advanced Breast Cancer

Intervention

Drug:
• Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC)
PH FDC SC is administered subcutaneously (SC) as a fixed non-weight-based dose. A loading dose of 1200 milligram (mg) pertuzumab, 600 mg trastuzumab, and 30,000 units of recombinant human PH20 hyaluronidase (rHuPH20) is given in the first cycle (1 cycle is 21 days). In subsequent cycles, maintenance doses of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units rHuPH20 are administered once every 3 weeks (Q3W).
• Pertuzumab IV
Pertuzumab is given as a fixed dose of 840 mg intravenous (IV) loading dose and then 420 mg IV for subsequent maintenance doses once every 3 weeks.
• Trastuzumab IV
Trastuzumab is given as an 8 milligram per kilogram (mg/kg) intravenous (IV) loading dose and then 6 mg/kg IV for subsequent maintenance doses once every 3 weeks.
• Trastuzumab Emtansine
Trastuzumab emtansine will be given at a dose of 3.6 mg/kg by intravenous (IV) infusion, once every 3 weeks.
• Investigator's Choice of Chemotherapy
Option 1: Docetaxel and carboplatin once every 3 weeks for 6 cycles; Option 2: Doxorubicin plus cyclophosphamide once every 3 weeks for 4 cycles, followed by a taxane (docetaxel once every 3 weeks for 4 cycles or paclitaxel once every week for 12 cycles); Option 3: Dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks for 4 cycles, followed by a taxane (docetaxel once every 3 weeks for 4 cycles or paclitaxel once every week for 12 cycles).

Procedure:
• Surgery
After completing their neoadjuvant therapy, participants will undergo surgical resection for early or locally advanced HER2+ breast cancer (if eligible for surgery). Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice. The surgery cannot be performed =2 weeks from the last systemic neoadjuvant therapy and must be performed =6 weeks after the last systemic neoadjuvant therapy.

Radiation:
• Radiotherapy
After surgery, radiotherapy is to be given as clinically indicated and as per local practice or institutional standards. The selected radiotherapy regimen should be initiated within 4 weeks after surgery.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Centro Oncologico Korben; Oncology	Ciudad Autonoma Buenos Aires
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	Cantonal Hospital Zenica; Department for Oncology	Zenica
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP
Bulgaria	Multiprofile Hospital for Active Treatment Uni Hospital; Department of medicinal oncology	Panagyurishte
Bulgaria	DDODIU-Plovdiv, EOOD; Third Internal Department	Plovdiv
Bulgaria	MHAT Nadezhda	Sofia
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Canada	North York General Hospital	Toronto	Ontario
Chile	Centro de Estudios Clínicos SAGA	Santiago
Chile	Clinica Vespucio	Santiago
Costa Rica	Hospital Metropolitano (Sede Lindora-Santa Ana); Centro de Cancer	San Jose
Costa Rica	Clinica CIMCA	San José
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San José
Croatia	Clinical Hospital Centre Zagreb	Zagreb
India	TATA Medical Centre; Medical Oncology	Kolkata	WEST Bengal
India	Saifee Hospital	Mumbai	Maharashtra
Kenya	International Cancer Institute (ICI)	Eldoret
Kenya	Aga Khan University Hospital	Nairobi
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Iem-Fucam	D.f.	Mexico CITY (federal District)
Mexico	Oncologico Potosino	San Luis Potosí	SAN LUIS Potosi
Peru	Instituto Regional de Enfermedades Neoplásicas del Sur; Centro de Inv. de Medicina Oncológica	Arequipa
Peru	Oncocenter Peru S.A.C.; Oncosalud	Lima
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	Tan Tock Seng Hospital; Oncology	Singapore
South Africa	Medical Oncology Centre of Rosebank; Oncology	Johannesburg
South Africa	Wilgers Oncology Centre	Pretoria
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia	Murcia
Spain	Hospital Clinico Universitario de Salamanca; Servicio de Oncologia	Salamanca
Turkey	Ankara City Hospital; Oncology	Ankara
Turkey	Gulhane Training and Research Hospital	Ankara
Turkey	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne
Turkey	Ba?c?lar Medipol Mega Üniversite Hastanesi; Oncology	Istanbul
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Chile,  Costa Rica,  Croatia,  India,  Kenya,  Korea, Republic of,  Mexico,  Peru,  Singapore,  South Africa,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Neoadjuvant Phase Drug Preparation Area		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)
Secondary	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		Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
Secondary	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		Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
Secondary	Duration of Treatment Administration Activities, According to Healthcare Professionals' Responses to Question 1 of the HCPQ - Neoadjuvant Phase Administering Treatment		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)
Secondary	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		Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
Secondary	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		Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
Secondary	Percentage of Healthcare Professionals by Their Responses to Question 11 of the HCPQ - Neoadjuvant Phase Administering Treatment		Day 1 of last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
Secondary	Percentage of Participants Achieving Pathologic Complete Response (pCR)	pCR is defined as eradication of invasive disease in the breast and axilla (i.e., ypT0/Tis ypN0), according to local pathologist assessment following the American Joint Committee on Cancer (AJCC) criteria.	Post-surgery (up to 27 weeks)
Secondary	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		Day 1 of Cycle 1 and Day 1 of last cycle of neoadjuvant treatment (Cycle 6 or 8; 1 cycle is 3 weeks)
Secondary	Health-Related Quality of Life Assessed by the EORTC QLQ-C30 Questionnaire Scores in Participants Treated with PH FDC SC During the Adjuvant Phase		Day 1 of Cycles 1, 3, 5, 8, and last cycle of adjuvant treatment (1 cycle is 3 weeks)
Secondary	Health-Related Quality of Life Assessed by the EORTC QLQ-C30 Questionnaire Scores in Participants Treated with Trastuzumab Emtansine During the Adjuvant Phase		Day 1 of Cycles 1, 7, and 14 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1 of the HCPQ - Adjuvant Phase Drug Preparation Area		Day 1 of Cycles 5 and 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	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		Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	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		Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	Duration of Treatment Administration Activities, According to Healthcare Professionals' Responses to Question 1 of the HCPQ - Adjuvant Phase Administering Treatment		Day 1 of Cycles 5 and 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	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		Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	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		Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	Percentage of Healthcare Professionals by Their Responses to Question 7 of the HCPQ - Adjuvant Phase Administering Treatment		Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	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		Day 1 of Cycle 8 of adjuvant treatment (1 cycle is 3 weeks)
Secondary	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)		From Baseline until surgery (up to 27 weeks)
Secondary	Incidence of Premature Withdrawal from Neoadjuvant Treatment with PH FDC SC or Pertuzumab IV and Trastuzumab IV		From Cycle 1 to last cycle (Cycle 6 or 8) of neoadjuvant treatment (1 cycle is 3 weeks)
Secondary	Number of Participants with Clinical Laboratory Test Abnormalities During the Neoadjuvant Treatment Phase		From Baseline until surgery (up to 27 weeks)
Secondary	Number of Participants with Vital Sign Abnormalities During the Neoadjuvant Treatment Phase		From Baseline until surgery (up to 27 weeks)
Secondary	Number of Participants with at Least One Adverse Event During the Adjuvant Treatment Phase, with Severity Determined According to the NCI CTCAE v5.0		From first dose post-surgery up to 9 months after the last dose of adjuvant treatment (up to 2 years)
Secondary	Incidence of Premature Withdrawal from Adjuvant Treatment with PH FDC SC		From Cycle 1 to last cycle (Cycle 12 or 14) of adjuvant treatment (1 cycle is 3 weeks)
Secondary	Incidence of Premature Withdrawal from Adjuvant Treatment with Trastuzumab Emtansine		From Cycle 1 to Cycle 14 (last cycle; 1 cycle is 3 weeks)
Secondary	Number of Participants with Clinical Laboratory Test Abnormalities During the Adjuvant Treatment Phase		From first dose post-surgery until the last dose of adjuvant treatment (up to 1.5 years)
Secondary	Number of Participants with Vital Sign Abnormalities During the Adjuvant Treatment Phase		From first dose post-surgery until the last dose of adjuvant treatment (up to 1.5 years)