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 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MO406282018-002153-30
• Study Type: interventional
• Target: 160
• Locations: 16 countries
• Sites: 38

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.

Conditions

HER2-Positive Early Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ)

  Question 1 of the Patient Preference Questionnaire (PPQ) asked participants the following question: "All things considered, which method of administration did you prefer?" The three available options for a participant's response were: IV, SC, or No preference. A point estimate with associated exact Clopper-Pearson binomial 95% confidence interval was calculated only for the percentage of participants who preferred PH FDC SC.

  Cycle 6 Day 1 (each cycle is 21 days)

Secondary Outcomes (44)

• 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)

  Cycle 6 Day 1 (each cycle is 21 days)

• 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)

  Cycle 6 Day 1 (each cycle is 21 days)

• 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)

  Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)

• 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

  Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)

• 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

  Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)

Study Arms (2)

A: P+H IV Followed by PH FDC SC

EXPERIMENTAL

In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose 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). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.

Drug: Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC); Drug: Pertuzumab IV; Drug: Trastuzumab IV

B: PH FDC SC Followed by P+H IV

EXPERIMENTAL

In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose 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). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.

Drug: Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC); Drug: Pertuzumab IV; Drug: Trastuzumab IV

Interventions

Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC) DRUG

PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg pertuzumab and 600 mg trastuzumab is then followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks (Q3W).

Also known as: PH FDC SC, Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, PHESGO™, RO7198574, RG6264

A: P+H IV Followed by PH FDC SC; B: PH FDC SC Followed by P+H IV

Pertuzumab IV DRUG

Pertuzumab will be administered intravenously (IV) as a fixed non-weight-based dose of 840-mg IV loading dose and then 420-mg IV maintenance dose Q3W.

Also known as: Perjeta®

A: P+H IV Followed by PH FDC SC; B: PH FDC SC Followed by P+H IV

Trastuzumab IV DRUG

Trastuzumab will be administered intravenously (IV) as an 8-mg/kg IV loading dose and then 6 mg/kg IV maintenance dose Q3W.

Also known as: Herceptin®

A: P+H IV Followed by PH FDC SC; B: PH FDC SC Followed by P+H IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (40)

Rocky Mountain Cancer Center - Lakewood (West)

Lakewood, Colorado, 80228, United States

Location

Illinois Cancer Care

Peoria, Illinois, 61615, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214-3728, United States

Location

Maryland Oncology Hematology

Rockville, Maryland, 20850, United States

Location

Texas Oncology - Dallas Presbyterian Hospital

Dallas, Texas, 75231, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology - Memorial City

Houston, Texas, 77024, United States

Location

USOR - Texas Oncology - San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

Texas Oncology- Northeast Texas

Tyler, Texas, 75702, United States

Location

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, C1284AEB, Argentina

Location

Instituto de Câncer E Transplante

Curitiba, Paraná, 80510-130, Brazil

Location

Clinicas Oncologicas Integradas - COI

Rio de Janeiro, Rio de Janeiro, 22290-160, Brazil

Location

Instituto de Ensino e Pesquisa Sao Lucas - IEP

São Paulo, São Paulo, 01236-030, Brazil

Location

Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA

São Paulo, São Paulo, 04014-002, Brazil

Location

Bradford Hill Centro de Investigaciones Clinicas

Recoleta, 8420383, Chile

Location

Hospital Hermanos Ameijeiras

La Habana, 10300, Cuba

Location

Instituto Nacional de Oncología y Radiología (INOR)

La Habana, 10400, Cuba

Location

KYS Sadesairaala; Syopatautien poliklinikka

Kuopio, 70210, Finland

Location

VAASAN KESKUSSAIRAALA; Onkologian poliklinikka

Vaasa, 65130, Finland

Location

Princess Margaret Hospital, Oncology; Department of Oncology

Hong Kong, Hong Kong

Location

Prince of Wales Hosp; Dept. Of Clinical Onc

Shatin, Hong Kong

Location

King Hussein Cancer Center

Amman, 11941, Jordan

Location

Bellevue Medical Center

El-Metn, 2241, Lebanon

Location

Hammoud Hospital

Saida, 6520, Lebanon

Location

Consultorio Privado (José Luis González Trujillo)

León, Guanajuato, Mexico

Location

Centro Médico Zambrano Hellion

Monterrey, Nuevo León, 66278, Mexico

Location

Cuidados oncologicos

Querétaro City, Querétaro, 76000, Mexico

Location

Centro Oncológico de Panamá

Panama City, 0801, Panama

Location

Centro Hemato Oncologico Panama

Panama City, 0832, Panama

Location

Hospital da Luz; Departamento de Oncologia Medica

Lisbon, 1500-650, Portugal

Location

Hospital de Santa Maria; Servico de Oncologia Medica

Lisbon, 1649-035, Portugal

Location

IPO do Porto; Servico de Oncologia Medica

Porto, 4200-072, Portugal

Location

National Center for Cancer Care and Research

Doha, 15054, Qatar

Location

King Fahad Medical City; Gastroentrology

Riyadh, 11525, Saudi Arabia

Location

Institute of Oncology and Radiology of Serbia

Belgrade, 11000, Serbia

Location

Clinical Centre Nis, Clinic for Oncology

Niš, 18000, Serbia

Location

Hospital General Universitario de Elche; Servicio de Oncologia

Elche, Alicante, 03203, Spain

Location

Hospital Universitario de Canarias;servicio de Oncologia

San Cristóbal de La Laguna, Tenerife, 38320, Spain

Location

Sodersjukhuset; Onkologkliniken

Stockholm, 118 83, Sweden

Location

Västmanlands sjukhus Västerås, Onkologkliniken

Västerås, 72189, Sweden

Location

Related Publications (2)

• O'Shaughnessy J, Sousa S, Cruz J, Fallowfield DL, Auvinen P, Pulido C, Cvetanovic A, Wilks S, Ribeiro L, Burotto M, Boulet T, Revelant V, Theron N, Trask P, Wahyudi L, Kirchmayer Machackova Z, Stamatovic L. Long-Term Safety and Efficacy of the Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients With HER2-Positive Early Breast Cancer in PHranceSCa, a Randomized, Open-Label Phase II Study. Clin Breast Cancer. 2025 Aug;25(6):554-559.e1. doi: 10.1016/j.clbc.2025.04.016. Epub 2025 May 3.

  PMID: 40461387 DERIVED

• 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.

  PMID: 34147014 DERIVED

MeSH Terms

Interventions

pertuzumab; Trastuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 17, 2018
• Study Start: December 19, 2018
• Primary Completion: February 24, 2020
• Study Completion: October 12, 2022
• Last Updated: January 2, 2024
• Results First Posted: April 26, 2021

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

BR (4); SA (1); ES (2); CL (1); ME (3); PT (3); PA (2); CU (2); HK (2); QA (1); SE (2); US (9); LE (2); FI (2); JO (1); AR (1)