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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

NCT03674112

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Inflammatory Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MO40628
  • SECONDARY ID: 2018-002153-30
  • NCT ID: NCT03674112

Conditions

  • HER2-Positive Early Breast Cancer

Interventions

DrugSynonymsArms
Pertuzumab and Trastuzumab FDC SCRO7198574A: Pertuzumab and Trastuzumab - IV Followed by FDC SC
Pertuzumab IVPerjetaA: Pertuzumab and Trastuzumab - IV Followed by FDC SC
Trastuzumab IVHerceptinA: Pertuzumab and Trastuzumab - IV Followed by FDC SC

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
A: Pertuzumab and Trastuzumab - IV Followed by FDC SCExperimentalIn the Treatment Cross-Over Period of the study, participants randomized to Arm A will first receive pertuzumab IV and trastuzumab IV for 3 treatment cycles followed by pertuzumab and trastuzumab FDC SC for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants will choose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
  • Pertuzumab and Trastuzumab FDC SC
  • Pertuzumab IV
  • Trastuzumab IV
B: Pertuzumab and Trastuzumab - FDC SC Followed by IVExperimentalIn the Treatment Cross-Over Period of the study, participants randomized to Arm B will first receive pertuzumab and trastuzumab FDC SC for 3 treatment cycles followed by pertuzumab IV and trastuzumab IV for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants will choose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment).
  • Pertuzumab and Trastuzumab FDC SC
  • Pertuzumab IV
  • Trastuzumab IV

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-positive 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Who Indicated They Preferred the Pertuzumab and Trastuzumab Fixed-Dose Combination Subcutaneous (FDC SC) Administration as Assessed in Question 1 of the Patient Preference Questionnaire
Time Frame:Cycle 6 Day 1 (each cycle is 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Participant-Assessed Satisfaction with Pertuzumab and Trastuzumab FDC SC, Based on Responses to Question 1 of the Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC)
Time Frame:Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Participant-Assessed Satisfaction with Pertuzumab and Trastuzumab IV, Based on Responses to Question 1 of the Therapy Administration Satisfaction Questionnaire - Intravenous (TASQ-IV)
Time Frame:Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Percentage of Participants Who Select Pertuzumab and Trastuzumab FDC SC for the Study Treatment Continuation Period
Time Frame:Cycle 7 Day 1 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Healthcare Professional (HCP) Perception of Time/Resource Use and Convenience of Each Study Regimen, Based on HCP Responses to the Healthcare Professional Questionnaire (HCPQ) - Treatment Room, by Individual Question
Time Frame:Day 1 of Cycles 1-6 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Healthcare Professional (HCP) Perception of Time/Resource Use and Convenience of Each Study Regimen, Based on HCP Responses to the HCPQ - Drug Preparation Room, by Individual Question
Time Frame:Day 1 of Cycles 1-6 (each cycle is 21 days)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status/QoL Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Physical Functioning Scale Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30)
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30
Time Frame:Baseline; Day 1 of Cycles 1, 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Issue:
Description:
Measure:Percentage of Participants with at Least One Adverse Event
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Percentage of Participants with at Least One Grade ≥3 Adverse Event, Severity Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0)
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Percentage of Participants with Heart Failure
Time Frame:Up to 3 years
Safety Issue:
Description:Heart failure severity will be assessed by the New York Heart Association (NYHA) Classification System For Heart Failure and the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0).
Measure:Percentage of Participants with Left Ventricular Ejection Fraction (LVEF) Decreases of At Least 10 Percentage Points From Baseline and to Below 50%
Time Frame:Baseline; Day 1 of Cycles 4, 7, and 11 (each cycle is 21 days); End of Treatment and Follow-Up visits (up to 3 years)
Safety Issue:
Description:
Measure:Percentage of Participants who Withdraw Prematurely from Study Treatment
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Percentage of Participants with an Adverse Event of Abnormal Targeted Vital Signs
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Percentage of Participants with an Adverse Event of Abnormal Physical Examination Findings
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Percentage of Participants with an Adverse Event of Abnormal Targeted Clinical Laboratory Test Results
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Kaplan-Meier Estimate of the Percentage of Participants in Invasive Disease-Free Survival
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Kaplan-Meier Estimate of the Percentage of Participants in Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Kaplan-Meier Estimate of the Percentage of Participants in Distant Disease-Free Survival
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival
Time Frame:Up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

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