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)

• ClinicalTrials.gov Identifier: NCT03498716
• Recruitment Status: Recruiting
• First Posted: April 17, 2018
• Last Update Posted: October 8, 2019
• Sponsor: Hoffmann-La Roche
• 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

Study Description

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 Design

• 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

Arms and Interventions

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

Outcome Measures

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).

Eligibility Criteria

• 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

Contacts and Locations

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

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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

More Information

• 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
• Last Update Posted: October 8, 2019
• Last Verified: October 2019

• 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; Albumin-Bound Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Atezolizumab; Epirubicin; Taxane; Antibodies; 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