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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)

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ClinicalTrials.gov Identifier: NCT03726879
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : March 20, 2019
Sponsor:
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Atezolizumab Drug: Placebo Drug: Doxorubicin Drug: Cyclophosphamide Drug: Paclitaxel Drug: Trastuzumab Drug: Pertuzumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
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
Actual Study Start Date : January 11, 2019
Estimated Primary Completion Date : September 23, 2020
Estimated Study Completion Date : February 8, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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 Name: Tecentriq

Drug: Doxorubicin
Doxorubicin will be administered as per the schedule specified in the respective arm.
Other Name: 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 Name: Taxol

Drug: Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.
Other Name: Herceptin

Drug: Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
Other Name: 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 Name: 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 Name: Taxol

Drug: Trastuzumab
Trastuzumab will be administered as per the schedule specified in the respective arm.
Other Name: Herceptin

Drug: Pertuzumab
Pertuzumab will be administered as per the schedule specified in the respective arm.
Other Name: Perjeta




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. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03726879


Contacts
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Contact: Reference Study ID Number: BO40747 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

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Sponsors and Collaborators
Hoffmann-La Roche
Chugai Pharmaceutical
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03726879     History of Changes
Other Study ID Numbers: BO40747
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Trastuzumab
Atezolizumab
Pertuzumab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors