First Line Atezolizumab, Paclitaxel, and Bevacizumab (Avastin®) in mTNBC

NCT04408118 | Completed Phase 2

• 2 other identifiers: MedOPP1502019-001503-20
• Study Type: interventional
• Target: 100
• Locations: 5 countries
• Sites: 26

Brief Summary

This is a multicenter, open-label, single-arm, phase II clinical trial to evaluate to evaluate the efficacy and safety of first line atezolizumab in combination with paclitaxel and bevacizumab (Avastin®) in patients with advanced or metastatic triple-negative breast cancer (mTNBC)

Conditions

Metastatic Breast Cancer; Advanced Breast Cancer; Triple Negative Breast Cancer

Keywords

breast cancer; metastatic breast cancer; triple negative breast cancer; HER2 negative; HR negative

Outcome Measures

Primary Outcomes (1)

• PFS (Progression-free Survival)

  From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.

  24 months

Secondary Outcomes (10)

• Efficacy (TTR)

  24 months

• Efficacy (ORR)

  24 months

• Efficacy (CBR)

  24 months

• Efficacy (DoR)

  24 months

• Efficacy (OS)

  24 months

Study Arms (1)

Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)

EXPERIMENTAL

All eligible patients will be treated with atezolizumab (840 mg) intravenously on days 1 and 15, Paclitaxel (90 mg/m2) on days 1, 8 and 15 via IV infusion and Bevacizumab (Avastin® 10mg/kg) intravenously on days 1 and 15. Treatment cycles and patient visits are organized in scheduled cycles of 28 days.

Drug: Atezolizumab; Drug: Paclitaxel; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Atezolizumab (840 mg) will be administered intravenously on Days 1 and 15. The first infusion of atezolizumab will be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.

Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)

Paclitaxel DRUG

Will be administered on days 1, 8 and 15 via IV infusion over 1 hour.

Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)

Bevacizumab DRUG

Will be administered intravenously over 30-90 minutes on Days 1 and 15.

Also known as: Avastin

Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form (ICF) prior to participation in any study-related activities.
• Male or female patients ≥ 18 years at the time of signing ICF.
• Ability to comply with the study protocol, in the investigator's judgment.
• Histologically confirmed TNBC -regardless of PD-L1 status- per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on local testing on the most recent analyzed biopsy. Triple-negative is defined as \<1% expression for estrogen receptor (ER) and progesterone receptor (PgR) as determined by immunohistochemistry (IHC), and negative for HER2 (0-1+ by immunohistochemistry \[IHC\] or 2+ and negative by in situ hybridization \[ISH\] test).
• Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
• No prior chemotherapy and/or targeted therapy and/or immunotherapy and/or antiangiogenic agent for triple negative MBC. Patients who have received (neo)adjuvant taxane-based chemotherapy and/or immunotherapy and/or an antiangiogenic agent are required to have a disease-free interval (DFI) of at least 12 months after completion of each of these treatments. For (neo)adjuvant non-taxane-based chemotherapy, a DFI of at least 6 months is required.
• Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the NCI-CTCAE v.5.0 (except for alopecia, grade ≤ 2 peripheral neuropathy, or other toxicities not considered a safety risk for the patient at investigator's discretion).
• Evidence of measurable disease or non-measurable disease as per RECIST v.1.1. Patients with only bone lesions are also eligible.
• Note: Patients for whom tumor biopsies cannot be obtained (e.g., inaccessible tumor or safety concern) may submit archived pathological material from either metastatic or primary sites, but the most recent tumor biopsy from the patient should be obtained when available.
• Note 2: Bone biopsies are only acceptable if performed on bone metastases with associated soft tissue mass, where the biopsy is performed on the soft tissue mass, and a decalcification process is not used. Cytology samples and decalcified bone specimens are unacceptable due to lack of validation studies.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of ≥12 weeks.
• Adequate hematologic and organ function within 14 days before the first study treatment on Cycle 1 Day 1 (C1D1), defined by the following parameters:
• a. Hematological: i. White blood cell (WBC) count \> 3.0 x 109/L. ii. Absolute neutrophil count (ANC) \> 1.5 X 109/L (without granulocyte colony-stimulating factor \[G-CSF\] support within 2 weeks prior to Cycle 1 Day1) iii. Lymphocyte count ≥ 0.5 x 109/L (500 cells/uL) iv. Platelet count ≥ 75.0 x 109/L (without transfusion within 2 weeks prior to Cycle 1 Day 1) v. Hemoglobin \> 9.0 g/dL (Patients may be transfused or receive erythropoietic treatment to meet this criterion).
• Note: Patients cannot be transfused platelets within 14 days prior to C1D1 to meet this criterion. The use of G-CSF within 14 days prior to C1D1 is also prohibited.

You may not qualify if:

• Known active uncontrolled or symptomatic central nervous system (CNS) metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they meet the following criteria:
• Evidence of measurable disease or non-measurable disease as per RECIST v.1.1.
• The patient has no history of intracranial hemorrhage.
• The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
• History of leptomeningeal disease.
• Uncontrolled tumor-related pain. Note 1: Patients requiring pain medication must be on a stable regimen at study entry.
• Note 2: Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrolment. Patients should be recovered from the effects of radiation.
• Active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis for a more comprehensive list of autoimmune diseases and immune deficiencies, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicum, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.

Sponsors & Collaborators

• MedSIR: lead
• Hoffmann-La Roche: collaborator

Study Sites (26)

Hopital Europeen Georges Pompidou

Paris, France

Location

Hôpital Tenon AP-HP

Paris, France

Location

Insitut de cancérologie Strasbourg Europe

Strasbourg, France

Location

Klinikum Dessau (MVZ) - Frauenheilkunde

Dessau, Germany

Location

University Hospital Essen

Essen, Germany

Location

Universitätsklinikum Mannheim

Mannheim, Germany

Location

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, Italy

Location

Hospital de Dénia-MarinaSalud

Denia, Alicante, Spain

Location

Hospital Universitario La Ribera

Alzira, Spain

Location

Hospital de Sant Joan Despí - Moises Broggi

Barcelona, Spain

Location

Hospital Universitari Dexeus

Barcelona, Spain

Location

Hospital Universitario Clínico San Cecilio

Granada, Spain

Location

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Ruber Juan Bravo

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

MD Anderson Cancer Center

Madrid, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, Spain

Location

Hospital Universitario San Juan de Alicante

Sant Joan d'Alacant, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Quirón Valencia

Valencia, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Barts Health NHS Trust

London, United Kingdom

Location

Royal Cornwall Hospitals Nhs Trust

Truro, United Kingdom

Location

Related Publications (2)

• Gion M, Blancas I, Cortez-Castedo P, Cortes-Salgado A, Marme F, Blanch S, Morales S, Diaz N, Calvo-Plaza I, Recalde S, Martinez-Bueno A, Ruiz-Borrego M, Llabres E, Taberner MT, de Laurentiis M, Garcia-Vicente S, Guerrero JA, Boix O, Rodriguez-Morato J, Sampayo-Cordero M, Antonarelli G, Perez-Garcia JM, Cortes J, Llombart-Cussac A; ATRACTIB Trial Investigators. Atezolizumab plus paclitaxel and bevacizumab as first-line treatment of advanced triple-negative breast cancer: the ATRACTIB phase 2 trial. Nat Med. 2025 Aug;31(8):2746-2754. doi: 10.1038/s41591-025-03734-3. Epub 2025 Jun 4.

  PMID: 40467896 DERIVED

• Agostinetto E, Eiger D, Punie K, de Azambuja E. Emerging Therapeutics for Patients with Triple-Negative Breast Cancer. Curr Oncol Rep. 2021 Mar 24;23(5):57. doi: 10.1007/s11912-021-01038-6.

  PMID: 33763756 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

atezolizumab; Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Antonio Llombart, PhD

  MedSIR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2020
• First Posted: May 29, 2020
• Study Start: October 5, 2020
• Primary Completion: December 7, 2023
• Study Completion: December 7, 2023
• Last Updated: June 4, 2024

Record last verified: 2023-12

Locations

FR (3); ES (17); GB (2); IT (1); DE (3)