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History of Changes for Study: NCT03726879
A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer (IMpassion050)
Latest version (submitted November 21, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 October 30, 2018 None (earliest Version on record)
2 November 26, 2018 Study Status and Contacts/Locations
3 December 18, 2018 Recruitment Status, Contacts/Locations and Study Status
4 January 15, 2019 Study Status and Contacts/Locations
5 February 4, 2019 Contacts/Locations and Study Status
6 February 25, 2019 Contacts/Locations and Study Status
7 March 18, 2019 Contacts/Locations and Study Status
8 April 8, 2019 Contacts/Locations and Study Status
9 April 29, 2019 Contacts/Locations, IPDSharing and Study Status
10 May 20, 2019 Study Status and Contacts/Locations
11 June 11, 2019 Study Status, Outcome Measures, Arms and Interventions, Contacts/Locations, Eligibility and Study Description
12 July 1, 2019 Study Status and Contacts/Locations
13 July 22, 2019 Contacts/Locations and Study Status
14 August 2, 2019 Contacts/Locations and Study Status
15 August 13, 2019 Outcome Measures, Contacts/Locations, Eligibility, Study Design and Study Status
16 September 4, 2019 Study Status
17 October 7, 2019 Contacts/Locations and Study Status
18 October 30, 2019 Contacts/Locations and Study Status
19 November 25, 2019 Contacts/Locations and Study Status
20 December 16, 2019 Contacts/Locations and Study Status
21 January 6, 2020 Contacts/Locations and Study Status
22 February 4, 2020 Contacts/Locations and Study Status
23 February 24, 2020 Contacts/Locations and Study Status
24 March 13, 2020 Study Status and Contacts/Locations
25 April 6, 2020 Study Status and Contacts/Locations
26 April 29, 2020 Contacts/Locations and Study Status
27 May 26, 2020 Study Status and Contacts/Locations
28 June 15, 2020 Contacts/Locations and Study Status
29 July 6, 2020 Contacts/Locations and Study Status
30 August 4, 2020 Study Status and Contacts/Locations
31 August 31, 2020 Contacts/Locations and Study Status
32 September 22, 2020 Study Status and Contacts/Locations
33 October 20, 2020 Study Status and Contacts/Locations
34 November 24, 2020 Study Status and Contacts/Locations
35 December 21, 2020 Contacts/Locations and Study Status
36 January 21, 2021 Recruitment Status, Study Status and Contacts/Locations
37 February 4, 2021 Recruitment Status, Contacts/Locations and Study Status
38 February 9, 2021 Recruitment Status, Contacts/Locations and Study Status
39 February 10, 2021 Study Status
40 March 11, 2021 Study Status, Study Design, Eligibility, Outcome Measures and Arms and Interventions
41 April 8, 2021 Study Status
42 May 11, 2021 Study Status
43 June 21, 2021 Contacts/Locations and Study Status
44 July 27, 2021 Study Status and Contacts/Locations
45 September 14, 2021 Study Status
46 November 2, 2021 Study Status
47 January 21, 2022
Quality Control Review has not concluded Returned: February 14, 2022
Outcome Measures, Study Status, Document Section and Contacts/Locations
48 February 25, 2022
Quality Control Review has not concluded Returned: March 22, 2022
Outcome Measures, Adverse Events, Study Status
49 March 24, 2022 Outcome Measures, Study Status
50 June 20, 2022 Study Status
51 July 26, 2022 Study Status
52 August 29, 2022 Study Status
53 November 21, 2022 Study Status
Comparison Format:

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Study NCT03726879
Submitted Date:  October 30, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: BO40747
Brief Title: A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer (IMpassion050)
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer
Secondary IDs:
Open or close this module Study Status
Record Verification: October 2018
Overall Status: Not yet recruiting
Study Start: November 21, 2018
Primary Completion: September 23, 2020 [Anticipated]
Study Completion: February 8, 2023 [Anticipated]
First Submitted: October 30, 2018
First Submitted that
Met QC Criteria:
October 30, 2018
First Posted: November 1, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
October 30, 2018
Last Update Posted: November 1, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators: Chugai Pharmaceutical
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This study (also known as IMpassion050) will evaluate the efficacy and safety of atezolizumab compared with placebo when given in combination with neoadjuvant dose-dense anthracycline (doxorubicin + cyclophosphamide) followed by paclitaxel + trastuzumab + pertuzumab (ddAC-PacHP) in patients with early HER2-positive breast cancer (T2-4, N1-3, M0).
Detailed Description:
Open or close this module Conditions
Conditions: Breast Cancer
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Care Provider)
Allocation: Randomized
Enrollment: 224 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Atezolizumab +ddAC-PacHP
Participants will receive atezolizumab 840 mg IV every 2 weeks (Q2W) for 4 cycles (Cycles 1-4) during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV), followed by atezolizumab 1200 mg IV every 3 weeks (Q3W) for 4 cycles (cycles 5-8) with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks (Cycles 5-8), trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W for 4 cycles (Cycles 5-8), and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W for 4 cycles (Cycles 5-8). During the adjuvant phase (Cycles 9-22), participants will continue to receive the following study treatments Q3W to complete up to 1 year of HER2-target therapy inclusive of therapy given both in the neoadjuvant and adjuvant setting: atezolizumab 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W, and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Other Names:
  • Tecentriq
Drug: Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.
Other Names:
  • Adriamycin
Drug: Cyclophosphamide
Cyclophosphamide will be administered as per the schedule specified in the respective arm.
Other Names:
  • Cytoxan
  • Neosar
Drug: Paclitaxel
Paclitaxel will be administered as per the schedule specified in the respective arm.
Other Names:
  • Taxol
Drug: Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.
Other Names:
  • Herceptin
Drug: Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
Other Names:
  • Perjeta
Placebo Comparator: Placebo + ddAC-PacHP
Participants will receive placebo 840 mg IV every 2 weeks (Q2W) for 4 cycles (Cycles 1-4) during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV), followed by placebo 1200 mg IV every 3 weeks (Q3W) for 4 cycles (cycles 5-8) with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks (Cycles 5-8), trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W for 4 cycles (Cycles 5-8), and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W for 4 cycles (Cycles 5-8). During the adjuvant phase (Cycles 9-22), participants will continue to receive the following study treatments Q3W to complete up to 1 year of HER2-target therapy inclusive of therapy given both in the neoadjuvant and adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with an initial 8-mg/kg IV loading dose) Q3W, and pertuzumab 420 mg IV (with an initial 840-mg IV loading dose) Q3W.
Drug: Placebo
Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.
Drug: Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.
Other Names:
  • Adriamycin
Drug: Cyclophosphamide
Cyclophosphamide will be administered as per the schedule specified in the respective arm.
Other Names:
  • Cytoxan
  • Neosar
Drug: Paclitaxel
Paclitaxel will be administered as per the schedule specified in the respective arm.
Other Names:
  • Taxol
Drug: Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.
Other Names:
  • Herceptin
Drug: Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
Other Names:
  • Perjeta
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percentage of Participants with Pathological Complete Response (pCR)
[ Time Frame: From randomization to approximately 24 months ]

pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer [AJCC] staging system, 8th edition) in the intent-to-treat (ITT) population.
Secondary Outcome Measures:
1. Percentage of Participants with pCR Based on Hormone Receptor Status
[ Time Frame: From randomization to approximately 24 months ]

pCR (ypT0/is ypN0) based upon hormone receptor status (estrogen receptor [ER]/progesterone receptor [PgR] positive or ER/PgR negative).
2. Percentage of Participants with pCR Based on PD-L1 Status
[ Time Frame: From randomization to approximately 24 months ]

pCR (ypT0/is ypN0) based upon PD-L1 status (IC 0; IC 1/2/3)
3. Event-Free Survival (EFS)
[ Time Frame: From randomization to first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause (up to approximately 48 months) ]

EFS defined as the time from randomization to the first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause, whichever occurs first, in all patients.
4. Disease-Free Survival (DFS)
[ Time Frame: From time from surgery to first documented disease recurrence or death from any cause (up to approximately 48 months) ]

DFS defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first, in all patients who undergo surgery.
5. Overall Survival (OS)
[ Time Frame: From randomization to date of death from any cause (up to approximately 48 months) ]

OS defined as the time from randomization to death from any cause in all patients.
6. Mean Changes From Baseline in Function (Role, Physical)
[ Time Frame: Baseline; Day 1 of Cycle 1-9, on Day 1 of every other cycle thereafter until Cycle 22; at the treatment discontinuation or early termination visit and follow up visit. Cycle 1-4, each cycle is 14 days. Cycle 5-22, each cycle is 21 days. ]

Mean changes from baseline score in function (role, physical) will be assessed by the functional scales of EORTC QLQ-C30.
7. Mean Changes From Baseline in Global Health Status
[ Time Frame: Baseline; Day 1 of Cycle 1-9, on Day 1 of every other cycle thereafter until Cycle 22; at the treatment discontinuation or early termination visit and follow up visit. Cycle 1-4, each cycle is 14 days. Cycle 5-22, each cycle is 21 days. ]

Mean changes from baseline will be assessed by the GHC/HRQoL scales of the EORTC QLQ-C30.
8. Percentage of Participants With Adverse Events
[ Time Frame: Baseline to end of study (approximately 48 months) ]

9. Maximum Serum Concentration (Cmax) of Atezolizumab
[ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]

Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
10. Minimum Serum Concentration (Cmin) of Atezolizumab
[ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]

Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
11. Trough Concentration (Ctrough) for Pertuzumab and Trastuzumab in Serum
[ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]

12. Percentage of Participants with Treatment-Emergent Anti-Drug Antibodies (ADAs) to Atezolizumab
[ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]

13. Percentage of Participants with Treatment-Emergent Anti-Drug Antibodies (ADAs) to Trastuzumab
[ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]

14. Percentage of Participants with Treatment-Emergent Anti-Drug Antibodies (ADAs) to Pertuzumab
[ Time Frame: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit. Cycle 1-4, each cycle is 14 days. Cycle 8-16, each cycle is 21 days. ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Confirmed diagnosis of HER2-positive breast cancer, and hormonal and PD-L1 status, as documented through central testing of a representative tumor tissue specimen
  • Primary breast tumor size of > 2 cm by radiographic measurement
  • Stage at presentation: T2-T4, N1-N3, M0 as determined by AJCC staging system, 8th edition
  • Pathologic confirmation of nodal involvement with malignancy must be determined by fineneedle aspiration or core-needle biopsy. Surgical excision of lymph nodes is not permitted.
  • Patients with multifocal tumors or multicentric tumors are eligible provided all discrete lesions are sampled and centrally confirmed as HER2-positive.
  • Patients with synchronous bilateral invasive disease are eligible so long as both lesions are HER2-positive.
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Baseline LVEF >= 55% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
  • Adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs
  • For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

  • Prior history of invasive breast cancer
  • Stage IV (metastatic) breast cancer
  • Prior systemic therapy for treatment of breast cancer
  • Previous therapy with anthracyclines or taxanes for any malignancy
  • Ulcerating breast cancer
  • Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
  • Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy
  • History of other malignancy within 5 years prior to screening, with the exception of those patients who have a negligible risk of metastasis or death
  • Cardiopulmonary dysfunction
  • Dyspnea at rest
  • Active or history of autoimmune disease or immune deficiency
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab/placebo, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab and/or pertuzumab, whichever occurs last
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: BO40747 www.roche.com/about_roche/roche_worldwide.htm
Telephone: 888-662-6728 (U.S. and Canada)
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, Maryland
Mercy Medical Center
Baltimore, Maryland, United States, 21202
United States, Missouri
HCA Midwest Division
Kansas City, Missouri, United States, 64132
United States, New York
New York University Medical Center PRIME; NYU Langone Medical Center
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Oregon
Providence Portland Medical Ctr
Portland, Oregon, United States, 97225
United States, Tennessee
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Vanderbilt
Nashville, Tennessee, United States, 37232
United States, Texas
Cancer Therapy and Research Center CTRC at UTHSCSA
San Antonio, Texas, United States, 78229
Brazil, BA
Hospital Sao Rafael - HSR
Salvador, BA, Brazil, 41253-190
Brazil, GO
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
Goiania, GO, Brazil, 74605-070
Brazil, RJ
Instituto Nacional de Cancer - INCa; Oncologia
Rio de Janeiro, RJ, Brazil, 20560-120
Brazil, RS
Hospital Sao Lucas - PUCRS
Porto Alegre, RS, Brazil, 90610-000
Hospital Nossa Senhora da Conceicao
Porto Alegre, RS, Brazil, 91350-200
Brazil, SP
Hospital Perola Byington
Sao Paulo, SP, Brazil, 01317-000
Canada, Alberta
Tom Baker Cancer Centre-Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Quebec
Jewish General Hospital; Research Unit
Montréal, Quebec, Canada, H3T 1E2
CHU de Québec - Hôpital du Saint-Sacrement
Quebec City, Quebec, Canada, G1S 4L8
Czechia
Masarykuv onkologicky ustav
Brno, Czechia, 656 53
Fakultni nemocnice Olomouc; Onkologicka klinika
Olomouc, Czechia, 779 00
Multiscan s.r.o.
Pardubice, Czechia, 532 03
Korea, Republic of
Gachon University Gil Medical Center
Incheon, Korea, Republic of, 21565
Korea University Anam Hospital
Seoul, Korea, Republic of, 02841
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Samsung Medical Center
Seoul, Korea, Republic of, 6351
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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