Clinical trial NCT03674112: A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer
Official title: A Randomized, Multicenter, Open-Label Cross-Over Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Patients With HER2-Positive Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2-Positive Early Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-09-17
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a Phase II, randomized, multicentre, multinational, open-label, cross-over study in adult patients who have completed neoadjuvant chemotherapy with neoadjuvant pertuzumab and trastuzumab and have undergone surgical treatment of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. The study will consist of two adjuvant treatment periods: a treatment cross-over period and a treatment continuation period. It will evaluate participant-reported preference for a subcutaneously administered fixed-dose combination formulation (FDC SC) of pertuzumab and trastuzumab compared with intravenously (IV) administered pertuzumab and trastuzumab formulations. The study will also evaluate participant-reported satisfaction with pertuzumab and trastuzumab FDC SC and health-related quality of life outcomes; healthcare professionals' perceptions of time/resource use and convenience of pertuzumab and trastuzumab FDC SC compared with pertuzumab and trastuzumab IV formulations; as well as the safety and efficacy of each study regimen.


Eligibility criteria: Inclusion Criteria:

Disease-specific criteria:

* Female or male with histologically confirmed, HER2-positive (HER2+) inflammatory, locally advanced or early-stage breast cancer who have received neoadjuvant pertuzumab and trastuzumab and have completed neoadjuvant chemotherapy and subsequently undergone surgery for their breast cancer.
* HER2+ breast cancer assessed at the local laboratory prior to initiation of neoadjuvant therapy. HER2+ status must be determined based on breast biopsy material obtained prior to neoadjuvant treatment and is defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥2 for the number of HER2 gene copies to the number of chromosome 17 copies.
* Hormone receptor status of the primary tumour determined by local assessment. Hormone receptor status may be either positive or negative.
* Completed all neoadjuvant chemotherapy and surgery. Adjuvant radiotherapy may be planned or ongoing at study entry and adjuvant hormone therapy is allowed during the study. Note that study treatment cannot be initiated within \<2 weeks of surgery but must be initiated ≤9 weeks from the last administration of systemic neoadjuvant therapy.
* No evidence of residual, locally recurrent or metastatic disease after completion of surgery. Patients with clinical suspicion of metastases must undergo radiological assessments per institutional practice to rule out distant disease.
* Wound healing after breast cancer surgery adequate per investigator's assessment to allow initiation of study treatment within ≤9 weeks of last systemic neoadjuvant therapy
* No adjuvant chemotherapy planned. Note that adjuvant hormonal treatment is allowed during the study.

General criteria:

* Ability to comply with the study protocol, in the investigator's judgment
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Intact skin at planned site of subcutaneous injections (thigh)
* Left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within 28 days of study randomization
* No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
* For women of childbearing potential: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating eggs, Women must remain abstinent or use non-hormonal contraceptive methods with a failure rate of \<1% per year, or two effective non-hormonal contraceptive methods during the study treatment periods and for 7 months after the last dose of study treatment
* For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, men must remain abstinent or use a condom during the study treatment periods and for seven months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period
* A negative serum pregnancy test must be available prior to randomization for women of childbearing potential

Exclusion Criteria:

Cancer-specific criteria:

* Stage IV (metastatic) breast cancer
* Current or prior history of active malignancy within the last five years. Appropriately treated non-melanoma skin cancer; in situ carcinomas, including cervix, colon, or skin; or Stage I uterine cancer within the last five years are allowed
* Previous systemic therapy for treatment or prevention of breast cancer, except neoadjuvant Perjeta, Herceptin and chemotherapy for current breast cancer

General criteria:

* Investigational treatment within four weeks of enrolment
* Serious cardiac illness or medical conditions
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome
* Inadequate bone marrow, renal and impaired liver function
* Current severe, uncontrolled systemic disease that may interfere with planned treatment
* Pregnant or breastfeeding, or intending to become pregnant during the study or within seven months after the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within seven days prior to initiation of study treatment
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in, and completion of, the study
* Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis
* Concurrent, serious, uncontrolled infections, or known infection with human immunodeficiency virus (HIV)
* Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins
* Current chronic daily treatment with corticosteroids

Primary outcomes:
measure: Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ)
timeFrame: Cycle 6 Day 1 (each cycle is 21 days)
Secondary outcomes:
measure: Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ)
timeFrame: Cycle 6 Day 1 (each cycle is 21 days)
measure: Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ)
timeFrame: Cycle 6 Day 1 (each cycle is 21 days)
measure: Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC)
timeFrame: Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)
measure: Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration
timeFrame: Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)
measure: Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness
timeFrame: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)
measure: Percentage of Participants by Their Responses to Question 10 of the TASQ-IV and TASQ-SC, Assessing Whether IV and SC Administration Have an Impact on the Amount of Time Participants Have to Talk to Their Nurse and/or Doctor About Their Illness
timeFrame: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)
measure: Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment
timeFrame: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)
measure: Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ
timeFrame: Cycle 6 Day 1 (each cycle is 21 days)
measure: Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room
timeFrame: Day 1 of Cycles 1-6 (each cycle is 21 days)
measure: Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room
timeFrame: Day 1 of Cycle 6 (each cycle is 21 days)
measure: Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room
timeFrame: Day 1 of Cycle 6 (each cycle is 21 days)
measure: Percentage of Healthcare Professionals (HCPs) by Their Responses to Question 8 of the HCPQ - Treatment Room
timeFrame: Day 1 of Cycle 6 (each cycle is 21 days)
measure: Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room
timeFrame: Day 1 of Cycles 1-6 (each cycle is 21 days)
measure: Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room
timeFrame: Day 1 of Cycle 6 (each cycle is 21 days)
measure: Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room
timeFrame: Day 1 of Cycle 6 (each cycle is 21 days)
measure: Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30)
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
measure: Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received
timeFrame: From Day 1 of Cycle 1 to the end of Cycle 3 of Cross-Over Period; from Day 1 of Cycle 4 to the end of Cycle 6 of Cross-Over Period (1 cycle is 21 days)
measure: Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods
timeFrame: From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days)
measure: Number of Participants With at Least One Event of Heart Failure With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods
timeFrame: From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days)
measure: Number of Participants With at Least One Event of Ejection Fraction Decreased With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods
timeFrame: Baseline; Day 1 of Cycles 4, 7, and 11 (each cycle is 21 days); End of Treatment Visit (up to 1 year)
measure: Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods
timeFrame: Pre-dose at Day 1 of Cycles 1 (baseline), 4, and 7, and end of treatment (up to 18 cycles; 1 cycle is 21 days)
measure: Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods
timeFrame: Pre-dose at Day 1 of Cycles 1 (baseline), 4, 7, 11, 15, and end of treatment (up to 18 cycles; 1 cycle is 21 days)
measure: Number of Participants With an Event for Overall Survival, Overall and by Treatment Sequence
timeFrame: Up to 3 years, 10 months
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Overall Survival, Overall and by Treatment Sequence
timeFrame: At 12, 24, and 36 months
measure: Number of Participants With an Event for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence
timeFrame: Up to 3 years, 10 months
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence
timeFrame: At 12, 24, and 36 months
measure: Number of Participants With an Event for Invasive Disease-Free Survival, Overall and by Treatment Sequence
timeFrame: Up to 3 years, 10 months
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival, Overall and by Treatment Sequence
timeFrame: At 12, 24, and 36 months
measure: Number of Participants With an Event for Distant Disease-Free Survival, Overall and by Treatment Sequence
timeFrame: Up to 3 years, 10 months
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Distant Disease-Free Survival, Overall and by Treatment Sequence
timeFrame: At 12, 24, and 36 months
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Center - Lakewood (West)
state: Colorado
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Rockville
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Dallas
country: United States
facility: Texas Oncology - Dallas Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Memorial City
state: Texas
city: San Antonio
country: United States
facility: USOR - Texas Oncology - San Antonio Northeast
state: Texas
city: Tyler
country: United States
facility: Texas Oncology- Northeast Texas
state: Texas
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Curitiba
country: Brazil
facility: Instituto de Câncer E Transplante
state: PR
city: Rio De Janeiro
country: Brazil
facility: Clinicas Oncologicas Integradas - COI
state: RJ
city: Sao Paulo
country: Brazil
facility: Instituto de Ensino e Pesquisa Sao Lucas - IEP
state: SP
city: Sao Paulo
country: Brazil
facility: Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
state: SP
city: Recoleta
country: Chile
facility: Bradford Hill Centro de Investigaciones Clinicas
city: La Habana
country: Cuba
facility: Hospital Hermanos Ameijeiras
city: La Habana
country: Cuba
facility: Instituto Nacional de Oncología y Radiología (INOR)
city: Kuopio
country: Finland
facility: KYS Sadesairaala; Syopatautien poliklinikka
city: Vaasa
country: Finland
facility: VAASAN KESKUSSAIRAALA; Onkologian poliklinikka
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital, Oncology; Department of Oncology
city: Shatin
country: Hong Kong
facility: Prince of Wales Hosp; Dept. Of Clinical Onc
city: Amman
country: Jordan
facility: King Hussein Cancer Center
city: El-Metn
country: Lebanon
facility: Bellevue Medical Center
city: Saida
country: Lebanon
facility: Hammoud Hospital
city: Leon
country: Mexico
facility: Consultorio Privado (José Luis González Trujillo)
state: Guanajuato
city: Monterrey
country: Mexico
facility: Centro Médico Zambrano Hellion
state: Nuevo LEON
city: Querétaro
country: Mexico
facility: Cuidados oncologicos
state: Queretaro
city: Panama
country: Panama
facility: Centro Oncológico de Panamá
city: Panama
country: Panama
facility: Centro Hemato Oncologico Panama
city: Lisboa
country: Portugal
facility: Hospital da Luz; Departamento de Oncologia Medica
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Oncologia Medica
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Doha
country: Qatar
facility: National Center for Cancer Care and Research
city: Riyadh
country: Saudi Arabia
facility: King Fahad Medical City; Gastroentrology
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia
city: Nis
country: Serbia
facility: Clinical Centre Nis, Clinic for Oncology
city: Elche
country: Spain
facility: Hospital General Universitario de Elche; Servicio de Oncologia
state: Alicante
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias;servicio de Oncologia
state: Tenerife
city: Stockholm
country: Sweden
facility: Sodersjukhuset; Onkologkliniken
city: Västerås
country: Sweden
facility: Västmanlands sjukhus Västerås, Onkologkliniken
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: O'Shaughnessy J, Sousa S, Cruz J, Fallowfield L, Auvinen P, Pulido C, Cvetanovic A, Wilks S, Ribeiro L, Burotto M, Klingbiel D, Messeri D, Alexandrou A, Trask P, Fredriksson J, Machackova Z, Stamatovic L; PHranceSCa study group. Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study. Eur J Cancer. 2021 Jul;152:223-232. doi: 10.1016/j.ejca.2021.03.047. Epub 2021 Jun 16.