| Study Objectives: |
Objectives and Endpoints
This study will evaluate the patient-reported preference of PH FDC SC administration in the home setting compared with the hospital setting during the cross-over period of adjuvant treatment in participants with early or locally advanced/inflammatory HER2+ breast cancer.
The administration of PH FDC SC in the home setting will be conducted by healthcare professionals (HCPs).
Specific primary and secondary objectives and corresponding endpoints for the study are outlined below.
Primary Objective Corresponding Endpoint
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To evaluate patient preference of PH FDC SC administration in the home setting during the cross-over period of the adjuvant phase of the study
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Corresponding endpoint: 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) (Appendix 5)
Secondary Objectives
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To evaluate the perception of HCPs of time/resource use and convenience of PH FDC SC compared to pertuzumab IV and trastuzumab IV (P+H IV) during the neoadjuvant phase of the study. Corresponding endpoint: Responses of HCPs to the Healthcare Professional Questionnaire (HCPQ) by individual questions in the neoadjuvant phase (Appendix 6 and Appendix 7)
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Collect pathological complete response (pCR) data post-surgery. Corresponding endpoint: Proportion of participants achieving pCR, defined a eradication of invasive disease in the breast and axilla (i.e., ypT0/Tis ypN0), according to local pathologist assessment following the AJCC criteria (FDA 2020)
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To evaluate Health-related Quality of Life (HRQoL) during the neoadjuvant phase of the study. Corresponding endpoint: HRQoL assessed by EORTC QLQ-C30 scores in the neoadjuvant phase (Appendix 8)
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To evaluate HRQoL with PH FDC SC administered during the adjuvant phase of the study. Corresponding endpoint: HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with PH FDC SC during the adjuvant phase (Appendix 8)
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To evaluate the perception of HCPs of time/resource use of PH FDC SC during the adjuvant cross-over period. Corresponding endpoint: Responses of HCPs to the HCPQ by individual questions in the adjuvant cross-over period (Appendix 9 and Appendix 10)
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To evaluate HRQoL for participants treated with trastuzumab emtansine IV during the adjuvant phase. Corresponding endpoint: HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with trastuzumab emtansine IV during the adjuvant phase (Appendix 8)
Secondary Safety Objectives
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To evaluate the safety and tolerability of PH FDC SC and P+H IV during the neoadjuvant phase of the study. Corresponding endpoint: Incidence, nature and severity of all adverse events (AEs), Grade ≥ 3 AEs, SAEs, and cardiac AEs (including left ventricular ejection fraction [LVEF] events) with severity determined according to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v5.0 (Appendix 14 and Appendix 16), Incidence of premature withdrawal from the neoadjuvant treatment with PH FDC SC and P+H IV, Targeted vital signs and physical findings, Targeted clinical laboratory test results
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To 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. Corresponding endpoint: Incidence, nature and severity of all AEs, Grade ≥ 3 AEs, SAEs and cardiac AEs (including LVEF events) with severity determined according to NCI CTCAE v5.0 (Appendix 14 and Appendix 16), Incidence of premature withdrawal from the adjuvant treatment with PH FDC SC, Targeted vital signs and physical findings, Targeted clinical laboratory test results
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To evaluate the safety and tolerability of trastuzumab emtansine IV during the adjuvant phase of the study. Corresponding endpoint: Incidence, nature and severity of all AEs Grade ≥ 3 AEs, SAEs and cardiac AEs (including LVEF events) with severity determined according to NCI CTCAE v5.0 (Appendix 14 and Appendix 16), Incidence of premature withdrawal from the treatment with trastuzumab emtansine IV, Targeted vital signs and physical findings, Targeted clinical laboratory test results
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| Laymans Summary: |
The purpose of this study is to evaluate the patient-reported preference for the pertuzumab and trastuzumab (PH) fixed-dose combination (FDC) for subcutaneous (SC) administration (PH FDC SC) in the home setting compared with the hospital setting in participants with early or locally advanced/inflammatory human epidermal growth factor receptor 2-positive (HER2+) breast cancer.
The SC delivery of biotherapeutics is well-established as a route of administration that is effective and well-tolerated across many therapeutic areas (Collins et al. 2020). It can offer several advantages over intravenous (IV) administration, including the convenience of self-administration, improved patient experience, reduced treatment burden and lower healthcare costs.
Moreover, the reduction in hospital time of the patient will reduce the patient's exposure to nosocomial pathogens and reduce the burden on healthcare systems.
This study will evaluate the patient-reported preference for PH FDC SC administration in the home setting compared with the hospital setting during the cross-over period of adjuvant treatment in participants with early or locally advanced/inflammatory HER2+ breast cancer.
The administration of PH FDC SC in the home setting will be conducted by healthcare professionals (HCPs).
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| Abstract of Study: |
A PHASE IIIB, MULTINATIONAL, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY TO EVALUATE PATIENT PREFERENCE FOR HOME
ADMINISTRATION OF A FIXED-DOSE COMBINATION OF PERTUZUMAB AND TRASTUZUMAB FOR SUBCUTANEOUS ADMINISTRATION IN PARTICIPANTS WITH EARLY OR LOCALLY ADVANCED/ INFLAMMATORY HER2-POSITIVE BREAST CANCER
PROTOCOL NUMBER: MO43110
VERSION NUMBER: 1
TEST COMPOUND(S):
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Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous (PH FDC SC)administration
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Pertuzumab IV
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Trastuzumab IV
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Trastuzumab emtansine IV
Objectives and Endpoints
This study will evaluate the patient-reported preference of PH FDC SC administration in the home setting compared with the hospital setting during the cross-over period of adjuvant treatment in participants with early or locally advanced/inflammatory HER2+ breast cancer.
The administration of PH FDC SC in the home setting will be conducted by healthcare professionals (HCPs).
Specific primary and secondary objectives and corresponding endpoints for the study are outlined below.
Primary Objective
-
To evaluate patient preference of PH FDC SC administration in the home setting during the cross-over period of the adjuvant phase of the study Corresponding endpoint: 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) (Appendix 5)
Secondary Objectives
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To evaluate the perception of HCPs of time/resource use and convenience of PH FDC SC compared to pertuzumab IV and trastuzumab IV (P+H IV) during the neoadjuvant phase of the study. Corresponding endpoint: Responses of HCPs to the Healthcare Professional Questionnaire (HCPQ) by individual questions in the neoadjuvant phase (Appendix 6 and Appendix 7)
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Collect pathological complete response (pCR) data post-surgery. Corresponding endpoint: Proportion of participants achieving pCR, defined a eradication of invasive disease in the breast and axilla (i.e., ypT0/Tis ypN0), according to local pathologist assessment following the AJCC criteria (FDA 2020)
-
To evaluate Health-related Quality of Life (HRQoL) during the neoadjuvant phase of the study. Corresponding endpoint: HRQoL assessed by EORTC QLQ-C30 scores in the neoadjuvant phase (Appendix 8)
-
To evaluate HRQoL with PH FDC SC administered during the adjuvant phase of the study. Corresponding endpoint: HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with PH FDC SC during the adjuvant phase (Appendix 8)
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To evaluate the perception of HCPs of time/resource use of PH FDC SC during the adjuvant cross-over period. Corresponding endpoint: Responses of HCPs to the HCPQ by individual questions in the adjuvant cross-over period (Appendix 9 and Appendix 10)
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To evaluate HRQoL for participants treated with trastuzumab emtansine IV during the adjuvant phase. Corresponding endpoint: HRQoL assessed by EORTC QLQ-C30 scores in the participants treated with trastuzumab emtansine IV during the adjuvant phase (Appendix 8)
Secondary Safety Objectives
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To evaluate the safety and tolerability of PH FDC SC and P+H IV during the neoadjuvant phase of the study. Corresponding endpoint: Incidence, nature and severity of all adverse events (AEs), Grade ≥ 3 AEs, SAEs, and cardiac AEs (including left ventricular ejection fraction [LVEF] events) with severity determined according to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v5.0 (Appendix 14 and Appendix 16), Incidence of premature withdrawal from the neoadjuvant treatment with PH FDC SC and P+H IV, Targeted vital signs and physical findings, Targeted clinical laboratory test results
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To 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. Corresponding endpoint: Incidence, nature and severity of all AEs, Grade ≥ 3 AEs, SAEs and cardiac AEs (including LVEF events) with severity determined according to NCI CTCAE v5.0 (Appendix 14 and Appendix 16), Incidence of premature withdrawal from the adjuvant treatment with PH FDC SC, Targeted vital signs and physical findings, Targeted clinical laboratory test results
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To evaluate the safety and tolerability of trastuzumab emtansine IV during the adjuvant phase of the study. Corresponding endpoint: Incidence, nature and severity of all AEs Grade ≥ 3 AEs, SAEs and cardiac AEs (including LVEF events) with severity determined according to NCI CTCAE v5.0 (Appendix 14 and Appendix 16), Incidence of premature withdrawal from the treatment with trastuzumab emtansine IV, Targeted vital signs and physical findings, Targeted clinical laboratory test results
Study Design
This is a phase IIIb, multinational, multicenter, randomized, open-label study to evaluate the patient preference of PH FDC SC administration in the home setting compared with the hospital setting during the cross-over period of adjuvant treatment in participants with early or locally advanced/inflammatory HER2+ breast cancer.
This study will consist of two phases.
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During the neoadjuvant phase, participants will be randomized in a 1:2 ratio to receive treatment in the hospital with either P+H IV plus chemotherapy (Arm A) or PH FDC SC plus chemotherapy (Arm B). Participants in both cohorts are scheduled to undergo surgery after the completion of neoadjuvant therapy. This could be after 6 or 8 cycles depending on the chosen neoadjuvant scheme. After surgery, local pathologists interpreting surgical specimens will determine whether pCR has been achieved following the AJCC criteria (FDA 2020).
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During the adjuvant phase, participants who achieve pCR after surgery will be treated with 2 cycles of PH FDC SC in the hospital. Then, participants will be randomized in a 1:1 ratio to two treatment arms in a cross-over manner, Arm C (3 cycles of PH FDC SC treatment in the hospital followed by another 3 cycles of PH FDC SC treatment in the home setting) and Arm D (3 cycles of PH FDC SC in the home setting followed by 3 cycles of PH FDC SC in the hospital). To complete a total of 18 cycles of treatment with pertuzumab and trastuzumab in the (neo)adjuvant setting, the last cycles of PH FDC SC will be administered in the hospital or in the home setting, as selected by the participant at the end of cross-over period. Participants can request to change from home administration to hospital administration (and vice-versa) during the treatment continuation period, but not during the treatment cross-over period. Participants with pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy and surgery will be treated with trastuzumab emtansine for 14 cycles (Arm E). Trastuzumab emtansine will be administered IV in the hospital as per prescribing information.
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