| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Early or locally advanced/inflammatory HER2-positive (HER2+) breast cancer. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Early or locally advanced HER2-positive (HER2+) breast cancer. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| 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 of pertuzumab and trastuzumab (PH) fixed-dose combination (FDC) for subcutaneous (SC) administration in the home setting during the cross-over period of the adjuvant phase of the study |
|
| E.2.2 | Secondary objectives of the trial |
● To evaluate the perception of healthcare professionals (HCPs) of time/resource use and convenience of PH FDC SC compared to PH IV during the neoadjuvant phase of the study
● Collect pathological complete response (pCR) data post-surgery
● To evaluate Health-related Quality of Life (HRQoL) during the neoadjuvant phase of the study and
● With PH FDC SC administered during the adjuvant phase of the study
● Evaluate the perception of HCPs of time/resource use of PH FDC SC during adjuvant cross-over period
● Evaluate HRQoL for participants treated with trastuzumab emtansine IV during the adjuvant phase
● Evaluate the safety and tolerability of PH FDC SC and P+H IV during neoadjuvant phase of the study
● Evaluate the safety and tolerability of PH FDC SC administered in the home setting and hospital setting during the cross-over period and the entire adjuvant treatment period
● Evaluate the safety and tolerability of trastuzumab emtansine IV during the adjuvant phase of the study
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
● Age >= 18 years
● Eastern Cooperative Oncology Group (ECOG) performance status 0-1
● Intact skin at planned site of SC injections
● Left ventricular ejection fraction (LVEF) >= 55% by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
● Negative human immunodeficiency virus (HIV) test at screening
● Negative hepatitis B surface antigen (HBsAg) test at screening
● Positive hepatitis B surface antibody (HBsAb) test at screening
● Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
● For female participants of childbearing potential: agreement to remain abstinent or use contraception and agree to refrain from donating eggs during the treatment period and for 7 months after the final dose of the study treatment
● For male participants: agreement to remain abstinent or use a condom, and agree to refrain from donating sperm during the treatment period and for 7 months after the final dose of study treatment to avoid exposing the embryo
Disease-specific Inclusion Criteria
● Female and male participants with stage II-IIIC early or locally advanced/inflammatory HER2+ breast cancer.
● Primary tumor > 2 cm in diameter, or node-positive disease
● HER2+ breast cancer confirmed by a local laboratory prior to study enrollment
● Hormone receptor status of the primary tumor determined by local assessment following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and updates
● Agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy, including the axillary nodes
● Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for local confirmation of HER2 and hormone receptor status following current ASCO/CAP guidelines
Inclusion Criteria for Treatment with Adjuvant PH FDC SC
● Completed the neoadjuvant phase of this study and underwent surgery, and achieved Pathologic complete response (pCR), defined as eradication of invasive disease in the breast and axilla according to the current American Joint Committee on Cancer (AJCC) staging system classification, and using the resected specimen by the local pathologist on the basis of guidelines to be provided in a Pathology Manual
● Adequate wound healing after breast cancer surgery per investigator’s assessment to allow initiation of study treatment within =< 9 weeks of last systemic neoadjuvant therapy
|
|
| E.4 | Principal exclusion criteria |
● Stage IV breast cancer
● History of concurrent or previously treated non-breast malignancies
● Participants who are pregnant or breastfeeding or intending to become pregnant during the study or within 7 months after the final dose of study treatments
● Treatment with investigational therapy within 28 days prior to initiation of study treatment
● Active, unresolved infections at screening requiring treatment
● Participants who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their International Normalized Ratio (INR)
● Serious cardiac illness or medical conditions
● History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
● Inadequate bone marrow function
● Impaired liver function
● Renal function with creatinine clearance < 50 mL/min using the Cockroft-Gault formula and serum creatinine > 1.5 x Upper limit of normal (ULN)
● Major surgical procedure unrelated to breast cancer within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment
● Current severe, uncontrolled systemic disease that may interfere with planned treatment
● Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual'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
● Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins or a history of severe allergic or immunological reactions, e.g., difficult to control asthma
● Current chronic daily treatment with corticosteroids
● Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol
Cancer-specific Exclusion Criteria for Neoadjuvant Phase
● Participants who have received any previous systemic therapy for treatment or prevention of breast cancer, or radiation therapy for the treatment of cancer
● Participants who have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsi- or contralateral breast cancer
● Participants with high-risk for breast cancer who have received chemopreventive drugs in the past are not allowed to enter the study
● Participants with multicentric breast cancer, unless all tumors are HER2+
● Participants with bilateral breast cancer
● Participants 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
● Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. Proportion of participants who preferred the administration of PH FDC SC in the home setting compared with the hospital setting in Question 1 of Patient Preference Questionnaire (PPQ) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. At the end of cross over period on Day 1, Cycle 8 of adjuvant phase |
|
| E.5.2 | Secondary end point(s) |
1. Responses of HCPs to the Healthcare Professional Questionnaire (HCPQ) by individual questions in the neoadjuvant phase
2. Proportion of participants achieving pCR, defined as eradication of invasive disease in the breast and axilla (i.e., ypT0/Tis ypN0), according to local pathologist assessment following the AJCC criteria
3. HRQoL assessed by European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ)-C30 scores in the neoadjuvant phase
4. HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with PH FDC SC during the adjuvant phase
5. Responses of HCPs to the HCPQ by individual questions in the adjuvant cross-over period
6. HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with trastuzumab emtansine IV during the adjuvant phase
7. Incidence, nature and severity of all Adverse events (AEs), Grade >= 3 AEs, Serious adverse event (SAEs), and cardiac AEs (including LVEF events) with severity determined according to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v5.0
8. Incidence of premature withdrawal from the neoadjuvant treatment with PH FDC SC and P+H IV
9. Incidence of premature withdrawal from the adjuvant treatment with PH FDC SC
10. Incidence of premature withdrawal from the treatment with trastuzumab emtansine IV
11. Targeted vital signs and Physical findings
12. Targeted clinical laboratory test results
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. HCPQs Neoadjuvant phase:
Day 1 of Cycle 1 up to 5 or 7 (depends on chosen neo scheme) for question 1;
Day 1 of the last cycle (6 or 8) for the rest
2. Post-surgery
3. Day 1 of Cycle 1 and last cycle (6 or 8, depends on chosen neoadjuvant scheme)
4. Those with pCR: Day 1 of Cycle 1, 3, 5, 8 and last cycle
5. HCPQs Adjuvant phase:
Day 1 of Cycle 5 and 8 for question 1;
Day 1 of Cycle 8 for the rest
6. Those without pCR (Arm E): Day 1 of Cycle 1, 7 and 14
7. Up to 6 to 9 months after the last dose in the adjuvant phase
8. Cycle 1 to Cycle 6 or 8 (depends on chosen neoadjuvant scheme)
9. From Cycle 1 until the last cycle (Cycle 12 or 14 according to the chosen neoadjuvant scheme)
10. From Cycle 1 to until the last cycle (Cycle 14)
11-12. Throughout the study up to 18 months
|
|
| 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 | Yes |
| 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 |
| Patient preference to home administration, Quality of life (QoL), time/resource use and convenience |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 5 |
| 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 | 56 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| 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 |
| Chile |
| Costa Rica |
| Peru |
| Singapore |
| Bosnia and Herzegovina |
| Brazil |
| Canada |
| India |
| Kenya |
| Korea, Republic of |
| Mexico |
| Russian Federation |
| South Africa |
| Bulgaria |
| Croatia |
| Czechia |
| Spain |
| Türkiye |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
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