Clinical Trials Logo

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
First received
Last updated
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
Health authority
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)

Study Design


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)
See also
  Status Clinical Trial Phase
Completed NCT01048918 - Characterization of Circulating Tumor Cells (CTC-s) in Patients With Locally Advanced or Metastatic Stage IV Breast Cancer
Recruiting NCT05383196 - Onvansertib + Paclitaxel In TNBC Phase 1/Phase 2
Recruiting NCT05744375 - Trastuzumab Deruxtecan in First-line HER2-positive Locally Advanced/MBC Patients Resistant to Trastuzumab+Pertuzumab Phase 2
Terminated NCT01837563 - Monitoring of Neoadjuvant Therapy in Locally-Advanced Breast Cancer N/A
Recruiting NCT03978663 - Three Fraction Radiation to Induce Immuno-Oncologic Response N/A
Active, not recruiting NCT04352777 - Impact of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2- Breast Cancer Phase 2
Recruiting NCT06064812 - A Phase I Clinical Trial of FWD1802 in Patients With ER+/HER2- BC. Phase 1
Recruiting NCT05963997 - A Study of Samuraciclib and Elacestrant in Participants With Metastatic or Locally Advanced HR+/HER2-negative Breast Cancer Phase 1/Phase 2
Recruiting NCT06080620 - The Choice of Treatment Methods and Efficacy of LABC N/A
Completed NCT05002868 - Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, in Patients With Solid Tumors Phase 1
Active, not recruiting NCT02595762 - A Study of Treatment Patterns and Outcomes in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Unresectable Locally Advanced or Metastatic Breast Cancer
Active, not recruiting NCT02965950 - The p53 Breast Cancer Trial Phase 2
Completed NCT01785992 - A Study of the Safety and Effectiveness of Irosustat When Added to an AI in ER+ve Locally Advanced or Metastatic Breast Cancer. Phase 2
Completed NCT00764036 - Study of Artesunate in Metastatic Breast Cancer Phase 1
Active, not recruiting NCT03685331 - HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer Phase 1
Completed NCT05021900 - Efficacy and Safety of Tenalisib (RP6530), a PI3K δ/γ and SIK3 Inhibitor, in Patients With Locally Advanced or Metastatic Breast Cancer Phase 2
Withdrawn NCT04088032 - Neoadjuvant Study of Abemaciclib, Durvalumab, and an Aromatase Inhibitor Early Stage Breast Cancer Early Phase 1
Completed NCT00455273 - Dynamic Breast MRI in Assessing Locally Advanced Breast Cancer
Terminated NCT04042051 - Copanlisib in Combination With T-DM1 in Pretreated Unresectable Locally Advanced or Metastatic HER2-positive Breast Cancer Phase 1
Recruiting NCT05582499 - Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy Phase 1/Phase 2