| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human epidermal growth factor receptor 2 (HER2)-positive Early Breast Cancer. |
|
| E.1.1.1 | Medical condition in easily understood language |
| HER2-positive breast cancer refers to breast cancer that tests positive for HER2 protein, which promotes the growth of cancer cells. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10065430 |
| E.1.2 | Term | HER-2 positive breast cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • To evaluate patient preference for pertuzumab and trastuzumab fixed-dose combination of pertuzumab and trastuzumab for subcutaneous use (FDC SC). |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate patient-assessed satisfaction with pertuzumab and trastuzumab (PH) FDC SC and intravenously administered Perjeta and Herceptin formulations (P+H IV)
• To evaluate patients’ choice of PH FDC SC for the treatment continuation period
• To evaluate health care professional (HCP) perception of time/resource use and convenience of PH FDC SC formulation
• To evaluate Global Health Status (GHS) / health-related quality of life (HRQoL) with PH FDC SC and P+H IV
• To evaluate the safety and tolerability of PH FDC SC and P+H IV during the study treatment cross-over period and the entire adjuvant treatment period (Treatment Cross-over Period + Treatment Continuation Period)
• To evaluate the safety of switching from PH FDC SC to P+H IV and from P+H IV to PH FDC SC
• To evaluate the long-term efficacy of the PH FDC SC and P+H IV |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Disease-specific criteria
- Female or male with histologically confirmed, HER2+ inflammatory, locally advanced or early-stage breast cancer who have received neoadjuvant Perjeta + Herceptin and have completed neoadjuvant chemotherapy and subsequently undergone surgery for their breast cancer
Note: The neoadjuvant chemotherapy regimen (including type and sequencing of selected agents) and the number of neoadjuvant Perjeta and Herceptin treatment cycles are at the discretion of the treating physician and patient. Subcutaneously administered Herceptin may have been used in the neoadjuvant setting. The use of any trastuzumab biosimilars in the neoadjuvant setting is not allowed
- 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 < two 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
- Age >= 18 years
- Ability to comply with the study protocol, in the investigator’s judgment
- Eastern Cooperative Oncology Group performance status 0 or 1
- Intact skin at planned site of subcutaneous injections (thigh)
- Left ventricular ejection fraction (LVEF) >= 55% measured by echocardiogram or multiple-gated acquisition scan within 28 days of study entry
- 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
|
|
| E.4 | Principal 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
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of patients who indicated they preferred pertuzumab and trastuzumab FDC SC administration as assessed using Question 1 of the Patient Preference Questionnaire |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1. Patient responses to the Therapy Administration Satisfaction Questionnaire – subcutaneous (TASQ-SC) and Therapy Administration Satisfaction Questionnaire – intravenous (TASQ-IV) will be assessed using the Question 1 of the TASQ
2. Proportion of patients who select pertuzumab and trastuzumab FDC SC for the study Treatment Continuation Period
3. HCP responses to the HCP Questionnaires, by individual question
4. Mean and mean changes from baseline score in HRQoL by cycle and between treatment arms as assessed by the GHS/HRQoL scale (items 29 and 30) of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30)
5. Change in EORTC QLQ-C30 scores from baseline and over time
6. Incidence, nature and severity of all Adverse events (AEs), >=Grade 3 AEs, Serious AEs and cardiac AEs (including LVEF events) with severity determined according to Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
7. Incidence of premature withdrawal from study treatment
8. Incidence of abnormal targeted vital signs and physical findings
9. Incidence of abnormal targeted clinical laboratory test results
10. Invasive disease-free survival
11. Invasive disease-free survival including second primary non-breast cancer
12. Distant disease-free survival
13. Overall survival |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. TASQ-SC: Day 1 of Cycle 6 (Arm A only) and Day 1 of Cycle 3 (Arm B only); TASQ-IV: Day 1 of Cycle 3 (Arm A only); Day 1 of Cycle 6 (Arm B only)
2. Up to 3 years from the date the last patient randomized
3. Day 1 of Cycle 1-6
4-5. At baseline (Day -7 to Day -1); Day 1 of Cycle 3 and 6; and at Cycle 15 or last treatment cycle and at follow-up visit
6-13.Up to 4 years
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Evaluate patient preference and satisfaction of subcutaneous administration of the fixed-dose combination of pertuzumab and trastuzumab |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Cuba |
| Hong Kong |
| Lebanon |
| Mexico |
| Panama |
| Qatar |
| Saudi Arabia |
| Serbia |
| United States |
| Jordan |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last Patient Last Visit (LPLV) which will occur three years after the last patient is randomized or the date at which the last data point required for the final statistical analysis or safety follow-up is received from the last patient, whichever occurs later. In addition, the Sponsor may decide to terminate the study at any time.
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
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