Evaluation of Healthcare and Patient Time Efficiency in Subcutaneous Fixed-Dose Combination of Pertuzumab and Trastuzumab for HER2-Positive Early Breast Cancer
- Trial ID
- 2023-509321-50-00
- Protocol
- ML42502
- Sponsor
- Roche Farma S.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to quantify healthcare professional (**HCP**) time savings and patient time savings when using a subcutaneous fixed-dose combination of **pertuzumab** and **trastuzumab** (**PH FDC SC**) compared to intravenous administration of Perjeta and Herceptin in the treatment of patients with **HER2-positive early breast cancer**. This is clinically relevant as it may lead to more efficient use of healthcare resources and improved patient experience by reducing the time spent in clinical settings.
Secondary objectives include:
- Quantifying the total patient time spent in the hospital for different administration routes.
- Quantifying resource utilization reduction in terms of consumables and drug wastage related to different administration routes.
- Describing the safety and tolerability of PH FDC SC, Perjeta IV + Herceptin IV, and Perjeta IV + Herceptin SC over the entire adjuvant treatment period.
Participants
The clinical trial focuses on patients diagnosed with **HER2-positive early breast cancer**. The study population includes both female and male participants, with an age requirement of 18 years or older. Participants are required to have a baseline left ventricular ejection fraction (LVEF) of at least 55%, as measured by echocardiogram or multiple-gated acquisition scan. The trial includes individuals who have completed neoadjuvant treatment with pertuzumab and trastuzumab in combination with chemotherapy and have undergone surgery for their breast cancer. Participants must have a confirmed total pathologic complete response, defined as the eradication of invasive disease in the breast and axilla. The trial population was selected based on specific inclusion criteria, including the ability to comply with the study protocol and an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. The sponsor has not provided information regarding the total number of participants. The study involves a vulnerable population, and both genders are included. Participants' hormone receptor status of the primary tumor is determined locally and may be either positive or negative. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not disclosed the total number of participants involved in the study.
Plans and Procedures
The clinical trial is designed to evaluate the time savings for healthcare professionals and patients when using a subcutaneous fixed-dose combination of **pertuzumab** and **trastuzumab** compared to intravenous administration in the treatment of HER2-positive early breast cancer. This study is a randomized, double-blind, controlled trial with an estimated duration from April 2021 to April 2025. Participants will be involved for a maximum treatment period of 72 weeks, with the possibility of early termination if they do not comply with the study protocol or experience significant adverse events.
The trial includes several key study visits. The initial inclusion visit involves screening participants to ensure they meet the eligibility criteria, such as having a baseline left ventricular ejection fraction of at least 55% and confirmed HER2-positive status. Follow-up visits are scheduled for each treatment cycle, specifically cycles 2 to 7, to measure healthcare professional time per patient and patient time per visit. These visits will assess the preparation and administration times for both intravenous and subcutaneous routes. The end-of-study visit will evaluate the overall safety and tolerability of the treatment, including the incidence and severity of adverse events.
Participants are expected to adhere to specific conditions, such as using effective contraception methods if of childbearing potential, and must not have undergone major surgery unrelated to breast cancer within 28 days prior to randomization. The primary endpoints focus on quantifying time savings for healthcare professionals and patients, while secondary endpoints include assessing hospital time per visit and the safety profile of the treatments. The trial aims to provide comprehensive data on the efficiency and safety of the subcutaneous fixed-dose combination therapy in the specified patient population.
Treatment
The clinical trial involves the administration of **Phesgo 1200 mg/600 mg solution for injection**, which is a combination of the active substances **trastuzumab** and **pertuzumab**. This pharmaceutical form is a solution for injection, administered via the injection route. The maximum daily dose is 1800 mg, with a total maximum dose of 32.4 g over a treatment period of up to 72 weeks. The administration is conducted under the supervision of healthcare professionals to ensure compliance and monitor any adverse effects.
Another treatment used in the trial is **Perjeta 420 mg concentrate for solution for infusion**, containing the active substance **pertuzumab**. This medication is provided as a concentrate for solution for infusion and is administered intravenously. The maximum daily dose is 840 mg, with a total maximum dose of 15.12 g over the same treatment period of 72 weeks. The infusion is performed in a clinical setting to ensure proper dosing and participant safety.
**Herceptin 150 mg powder for concentrate for solution for infusion** is also utilized in the study. The active substance in this formulation is **trastuzumab**. It is prepared as a solution for infusion and administered intravenously. The dosing is based on body weight, with a maximum daily dose of 8 mg/kg and a total maximum dose of 144 mg/kg over 72 weeks. The preparation and administration are conducted by trained personnel to maintain dosing accuracy and participant safety.
Additionally, **Herceptin 600 mg solution for injection in vial** is included in the trial. This formulation also contains the active substance **trastuzumab** and is administered subcutaneously. The maximum daily dose is 600 mg, with a total maximum dose of 10800 mg over the treatment period. The subcutaneous administration is performed by healthcare professionals to ensure proper technique and monitor for any adverse reactions.
Lastly, the trial includes **Phesgo 600 mg/600 mg solution for injection**, another combination of **trastuzumab** and **pertuzumab**. This solution is administered via injection, with a maximum daily dose of 1200 mg and a total maximum dose of 21.6 g over 72 weeks. The administration is closely monitored to ensure participant compliance and safety throughout the study.
Efficacy
Efficacy in the clinical trial will be assessed using specific primary and secondary endpoints. The primary endpoints include the average healthcare professional (HCP) time per patient per visit, measured for cycles 2-7 in the adjuvant setting. This will be evaluated for different administration route processes, with time disaggregated per pre-specified task and per HCP, such as oncologist, nurse, pharmacist, and others. The tasks include preparation times and administration times for both intravenous (IV) and subcutaneous (SC) administration routes. Additionally, the average patient time per visit will be measured, focusing on patient chair time and treatment room time.
Secondary endpoints will assess the average patient hospital time per visit, measured for cycles 2-7, and the average quantity of each consumable used per patient visit. This includes milligrams wasted from partly-used vials. Safety and tolerability will also be described based on the incidence, nature, and severity of adverse events (AEs), including those of Grade 3 or higher, serious adverse events (SAEs), and cardiac AEs such as left ventricular ejection fraction (LVEF) events. The incidence of premature withdrawal from study treatment, targeted vital signs, physical findings, and clinical laboratory test results will also be monitored.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed Informed Consent Form
- Age ≥ 18 years at time of signing Informed Consent Form
- Ability to comply with the study protocol, in the investigator’s judgment
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Female and male patients with locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed node positive invasive breast cancer with initial diagnosis TNM staging any T (except T0) plus N+ and M0
- Completed neoadjuvant treatment with pertuzumab and trastuzumab in combination with chemotherapy according to routine clinical practice, and have undergone surgery for their breast cancer. Note that study treatment cannot be initiated within < 2 weeks from surgery but must be initiated ≤ 8 weeks from surgery
- Confirmed tpCR (total pathologic complete response), defined as eradication of invasive disease in the breast and axilla (i.e., ypT0/is ypN0), according to local pathologist assessment
- HER2-positive breast cancer confirmed by a local laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by 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 signals for chromosome 17 copies
- Hormone receptor status of the primary tumour determined by local assessment. Hormone receptor status may be either positive (i.e. ER-positive and/or PgR positive) or negative (i.e. ER-negative and PgR-negative)
- Baseline LVEF ≥ 55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
- For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective nonhormonal contraceptive method with a failure rate of < 1% per year, or two effective nonhormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of highly effective nonhormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom with a spermicidal product during the treatment period and for 7 months after the last dose of HER2-targeted therapy to avoid exposing the embryo. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
- A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women < 12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)
- 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
Exclusion Criteria
- Stage IV (metastatic) breast cancer
- Any amount of residual disease in both breast and residual nodes, other than ypT0/is ypN0, will not be allowed to enter the study
- Neoadjuvant treatment with trastuzumab alone
- Already started systemic anti-HER2 treatment for their breast cancer in the adjuvant setting
- Need for chemotherapy during the adjuvant setting
- Current or prior history of active malignancy (other than current breast cancer) within the last five years. Appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin or 3) stage I uterine cancer within the last five years are allowed. A patient with previous invasive non-breast cancer is eligible provided he/she has been disease free for more than 5 years
- Patients who have a past history of ductal carcinoma in situ (DCIS), infiltrative ductal carcinoma (IDC), lobular carcinoma in situ (LCIS) or infiltrative lobular carcinoma (ILC) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast
- Patients with bilateral breast cancer
- Patients 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. ● Patients with clinically negative axilla (by physical examination and radiographic imaging) may undergo a core or needle biopsy procedure prior to neoadjuvant systemic therapy if in keeping with local practice
- Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy
- Treatment with any investigational drug within 28 days prior to randomization
- Serious cardiac illness or medical conditions including, but not confined to, the following: ● History of NCI CTCAE (v5) Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II ● High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block) ● Serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality ● Angina pectoris requiring anti-anginal medication ● Clinically significant valvular heart disease ● Evidence of transmural infarction on ECG ● Evidence of myocardial infarction within 12 months prior to starting neoadjuvant treatment ● Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100 mmHg)
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
- Cumulative prior anthracycline exposure to > 360 mg/m2 of doxorubicin or its equivalent
- Inadequate bone marrow function, defined as: ● Absolute neutrophil count < 1.5 x 109/L ● Platelet count < 100 x 109/L ● Hemoglobin < 9 g/dL
- Impaired liver function, defined as: ● Serum (total) bilirubin > 1.25 x upper limit of normal (ULN). In case of Gilbert’s syndrome: a total bilirubin of 2 x ULN is permitted. ● Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.25 x ULN ● Albumin < 25 g/L
- Inadequate renal function with serum creatinine > 1.5 x ULN
- Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders)
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy ● Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study drug
- 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 (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis
- Concurrent, serious, uncontrolled infections, or known infection with HIV
- Known hypersensitivity to study drugs, excipients, and/or murine proteins
- Current chronic daily treatment with corticosteroids (dose > 10 mg methylprednisolone or equivalent excluding inhaled steroids)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 21 Apr 2021 | 34 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Phesgo 1200 mg/600 mg solution for injection | Test | SOLUTION FOR INJECTION | INJECTION | 1800 | 72 | PRD8600161 |
Perjeta 420 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 840 | 72 | PRD2154581 |
Herceptin 600 mg solution for injection in vial | Test | SOLUTION FOR INJECTION IN VIAL | SUBCUTANEOUS | 600 | 72 | PRD2154036 |
Phesgo 600 mg/600 mg solution for injection | Test | SOLUTION FOR INJECTION | INJECTION | 1200 | 72 | PRD8601830 |
Herceptin 150 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 8 | 72 | PRD2154035 |