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A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer (IMpassion030)

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ClinicalTrials.gov Identifier: NCT03498716
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : November 28, 2018
Sponsor:
Collaborators:
Breast International Group
Alliance Foundation Trials (AFT)
Institut Jules Bordet/Clinical Trials Support Unit (IJB/CTSU)
Frontier Science and Technology Research Foundation Inc (FS)
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the efficacy, safety, and pharmacokinetics of adjuvant atezolizumab in combination with paclitaxel, followed by atezolizumab, dose-dense doxorubicin or epirubicin (investigator's choice), and cyclophosphamide, compared with paclitaxel followed by dose-dense doxorubicin or epirubicin (investigator's choice) and cyclophosphamide alone in patients with Stage II-III TNBC (Triple Negative Breast Cancer)

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Drug: Atezolizumab Drug: Paclitaxel Drug: Dose-dense Doxorubicin or dose-dense Epirubicin Drug: Cyclophosphamide Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Open-Label Study Comparing Atezolizumab (Anti PD-L1 Antibody) in Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone in Patients With Operable Triple Negative Breast Cancer
Actual Study Start Date : August 2, 2018
Estimated Primary Completion Date : January 15, 2022
Estimated Study Completion Date : December 29, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Atezolizumab + Chemotherapy

Participants will receive atezolizumab (in combination with chemotherapy as described below) every 2 weeks for 10 doses, followed by atezolizumab maintenance therapy every 3 weeks to complete 1 year of treatment from the first dose

Chemotherapy will consist of paclitaxel every week for 12 weeks, followed by dose-dense doxorubicin +cyclophosphamide or dose-dense epirubicin + cyclophosphamide every 2 weeks, for 4 doses supported with Granulocyte Colony-Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

Drug: Atezolizumab

Atezolizumab will be administered by IV, 840 mg every 2 weeks, for 10 doses.

Atezolizumab maintenance will be administered by IV, 1200 mg every 3 weeks to complete 1 year


Drug: Paclitaxel
Paclitaxel will be administered by IV, 80 mg/m^2 every week for 12 weeks.

Drug: Dose-dense Doxorubicin or dose-dense Epirubicin

Dose-dense doxorubicin will be administered by IV, 60 mg/m^2 every 2 weeks for a total of 4 doses.

Or

Dose-dense epirubicin will be administered by IV, (90 mg/m^2) every 2 weeks for a total of 4 doses


Drug: Cyclophosphamide
Cyclophosphamide will be administered by IV, 600 mg/m^2 every 2 weeks for 4 doses

Active Comparator: Chemotherapy
Chemotherapy will consist of paclitaxel every week for 12 weeks, followed by dose-dense doxorubicin +cyclophosphamide or dose-dense epirubicin + cyclophosphamide every 2 weeks, for 4 doses supported with Granulocyte Colony-Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Drug: Paclitaxel
Paclitaxel will be administered by IV, 80 mg/m^2 every week for 12 weeks.

Drug: Dose-dense Doxorubicin or dose-dense Epirubicin

Dose-dense doxorubicin will be administered by IV, 60 mg/m^2 every 2 weeks for a total of 4 doses.

Or

Dose-dense epirubicin will be administered by IV, (90 mg/m^2) every 2 weeks for a total of 4 doses


Drug: Cyclophosphamide
Cyclophosphamide will be administered by IV, 600 mg/m^2 every 2 weeks for 4 doses




Primary Outcome Measures :
  1. Invasive Disease-Free Survival (iDFS) [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years). ]

    iDFS events are defined as follows:

    1. Ipsilateral invasive breast tumor recurrence
    2. Ipsilateral local-regional invasive breast cancer recurrence
    3. Ipsilateral second primary invasive breast cancer
    4. Contralateral invasive breast cancer
    5. Distant recurrence
    6. Death attributable to any cause


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Randomization to death from any cause through the end of study (approximately 7 years) ]
  2. Disease-Free Survival (DFS) [ Time Frame: Randomization until the first occurrence of an DFS event, through the end of study (approximately 7 years) ]
    DFS is defined as any event of the primary endpoint and new diagnosis of an ipsilateral or contralateral non-invasive breast cancer.

  3. Recurrence-Free Interval (RFI) [ Time Frame: Randomization until local, regional, or distant disease recurrence of breast cancer, through the end of study (approximately 7 years) ]
  4. Distant RFI [ Time Frame: Randomization until distant disease recurrence, through the end of study (approximately 7 years) ]
  5. Percentage of participants with adverse events [ Time Frame: Baseline to end of study (approximately 7 years) ]
    Safety Objective

  6. Serum concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hour), 30 minutes post-infusion on Week 1 Day 1 (infusion length = 60 minutes); pre-infusion on Day 1 of Weeks 5, 9, 13, 21, 33 and 45; at treatment discontinuation (up to approximately 1 year), 120 days after last dose ]
  7. Invasive Disease-Free Survival (iDFS) in PDL1- Selected Patients [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  8. Invasive Disease-Free Survival (iDFS) in Node- Positive Disease [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  9. Invasive Disease Free Survival (iDFS) including second primary non-breast invasive cancer [ Time Frame: Randomization until the first occurrence of iDFS event or death, through the end of study (approximately 7 years) ]
  10. Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Updated: Pre-infusion (0 hour) on Day 1 of Weeks 1, 5, 9, 13, 21, 33 and 45; at treatment discontinuation (up to Week 51), 120 days after last dose ]
  11. Mean changes from baseline in patient-reported function (role, physical) [ Time Frame: Baseline, Cycle 4 Day 1, Day 1 of every other cycle until Cycle 16 (cycle = 21 days), at the end of treatment/discontinuation visit ((up to approximately 1 year), and during Study Follow-up (up to approximately 7 years). ]
    Mean changes from baseline score in role, physical function will be assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30)

  12. Mean changes from baseline in patient-reported health-related quality of life (HRQoL) [ Time Frame: Time Frame: Baseline, Cycle 4 Day 1, Day 1 of every other cycle until Cycle 16 (cycle = 21 days), at the end of treatment/discontinuation visit (up to approximately 1 year), and during Study Follow-up (up to approximately 7 years). ]
    Mean changes from baseline score in HRQoL will be assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30).



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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:

  • Non-metastatic operable Stage II-III breast cancer
  • Histologically documented TNBC (Triple Negative Breast Cancer)
  • Confirmed tumor PD-L1 evaluation as documented through central testing of a representative tumor tissue specimen
  • Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
  • Adequate hematologic and end-organ function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
  • No more than 8 weeks (56 days) may elapse between definitive breast surgery and randomization.
  • Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical resection in paraffin blocks (preferred) or at least 25 unstained slides.

Exclusion Criteria

  • Prior history of invasive breast cancer
  • For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (e.g., neoadjuvant or adjuvant), including, but not limited to, chemotherapy, anti-HER2 therapy.
  • Previous therapy with anthracyclines or taxanes for any malignancy
  • Cardiopulmonary dysfunction
  • Prior malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Urinary outflow obstruction
  • Active tuberculosis
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment or within 5 months following the last dose of Atezolizumab (for patients randomized to Atezolizumab)
  • Prior allogeneic stem cell or solid organ transplant
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study

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): NCT03498716


Contacts
Contact: Reference Study ID Number: WO39391 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 401 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Breast International Group
Alliance Foundation Trials (AFT)
Institut Jules Bordet/Clinical Trials Support Unit (IJB/CTSU)
Frontier Science and Technology Research Foundation Inc (FS)
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03498716     History of Changes
Other Study ID Numbers: WO39391
2016-003695-47 ( EudraCT Number )
BIG 16-05 ( Other Identifier: Breast International Group (BIG) )
AFT-27 ( Other Identifier: Alliance Foundation Trials )
ALEXANDRA ( Other Identifier: Breast International Group (BIG) )
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018

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

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Atezolizumab
Taxane
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Epirubicin
Antibodies
Antibodies, Monoclonal
Lenograstim
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