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Invasive Breast CarcinomaPhase 2NCT02883062

Carboplatin and Paclitaxel With or Without Atezolizumab Before Surgery in Treating Patients With Newly Diagnosed, Stage II-III Triple-Negative Breast Cancer

A Phase 2 study testing Atezolizumab, Biospecimen Collection and Carboplatin in people with Invasive Breast Carcinoma and Stage II Breast Cancer AJCC v6 and v7, run by National Cancer Institute (NCI) at 14 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This phase II trial studies how well carboplatin and paclitaxel with or without atezolizumab before surgery works in treating patients with newly diagnosed, stage II-III triple negative breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Atezolizumab, Biospecimen Collection and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
14 sitesUnited States
Study dates
2 Aug 2017to 30 Sep 2027
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed new diagnosis of breast cancer
  • Estrogen receptor (ER) and progesterone receptor (PR) < Allred score of 3 or =< 5% positive staining cells in the invasive component of the tumor (provided the patient is being treated as triple negative breast cancer)
  • Human epidermal growth factor receptor 2 (HER2) negative by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) staining 0 or 1+ according to National Comprehensive Cancer Network (NCCN) guidelines
  • Clinical stage T2-T4c, any N, M0 primary tumor by American Joint Committee on Cancer (AJCC) 7th edition clinical staging
  • Eligible for neoadjuvant chemotherapy
  • No prior therapy for this disease
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  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 2,500/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 150,000/mcL
  • Hemoglobin >= 10 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • Creatinine clearance >= 30 mL/min/1.73 m^2 by Cockcroft-Gault
  • International normalized ratio (INR) =< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
  • Activated partial thromboplastin time (aPPT) =< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
  • Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 180 days after the last dose of paclitaxel; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign an Institutional Review Board (IRB) approved written informed consent document

Who cannot join

  • Known metastatic disease
  • Invasive cancer in the contralateral breast
  • Patients with a previous history of non-breast malignancy are eligible only if they meet the following criteria for a cancer survivor: (1), and (2)
  • Has undergone potentially curative therapy for all prior malignancies
  • Has been considered disease-free for at least 1 year (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix)
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
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  • Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1
  • Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to cycle 1, day 1
  • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
  • Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., osteoporosis) is allowed
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in study
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
  • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Patients with active tuberculosis (TB) are excluded
  • Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1
  • Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study with the exception of the planned breast cancer surgery that is part of the trial design
  • Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab
  • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks prior to cycle 1, day 1 or at any time during the study
  • Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumab
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (including symptomatic sinus bradycardia), or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have:
  • A stable regimen of highly active anti-retroviral therapy (HAART)
  • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
  • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests
  • Pregnant women are excluded from this study because atezolizumab is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab; these potential risks may also apply to other agents used in this study

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites
  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

Other trials in United States

About this study

Official title: Randomized Phase 2 Study of Neoadjuvant Chemotherapy, Carboplatin and Paclitaxel, With or Without Atezolizumab in Triple Negative Breast Cancer (TNBC)

This phase II trial studies how well carboplatin and paclitaxel with or without atezolizumab before surgery works in treating patients with newly diagnosed, stage II-III triple negative breast cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carboplatin and paclitaxel with or without atezolizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To test the hypothesis that the combination of chemotherapy and atezolizumab will increase tumor infiltrating lymphocyte (TIL) percentage compared to chemotherapy alone in patients with newly diagnosed triple negative breast cancer (TNBC) being treated with neoadjuvant chemotherapy.

II. To test the hypothesis that the combination of chemotherapy and atezolizumab will increase the pathologic complete response (pCR) rate compared to chemotherapy alone in patients with newly diagnosed TNBC being treated with neoadjuvant chemotherapy.

SECONDARY OBJECTIVE:

  1. To evaluate the safety of the treatment combination of atezolizumab + carboplatin + paclitaxel.

EXPLORATORY OBJECTIVES:

  1. To evaluate potential biomarkers of response to chemotherapy in combination with atezolizumab in patients with newly diagnosed TNBC.

II. To evaluate the impact of chemotherapy in combination with atezolizumab on the immune response in patients with newly diagnosed TNBC.

III. To evaluate the impact of chemotherapy in combination with atezolizumab on neoantigen-specific T cell responses in patients with newly diagnosed TNBC.

IV. To evaluate the impact of chemotherapy in combination with atezolizumab on long-term clinical endpoints such as overall survival (OS) and disease-free survival (DFS) in patients with newly diagnosed TNBC.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM A: Patients receive carboplatin intravenously (IV) over 30 minutes once every 3 weeks (Q3W) and paclitaxel IV over 1 hour once weekly (QW). Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

In both arms, within 3-6 weeks, patients undergo mastectomy or lumpectomy. Patients also undergo the collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up at 6 months and 1 year.

Being tested
Atezolizumab, Biospecimen Collection, Carboplatin, Lumpectomy, Mastectomy
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • LumpectomyProcedure or surgery

    Also called Lumpectomy of Breast, Partial Mastectomy

    Undergo lumpectomy

  • MastectomyProcedure or surgery

    Also called Mammectomy

    Undergo mastectomy

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

Study groups in NCT02883062
Study groupRoleWhat they receive
Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)Active comparatorPatients receive carboplatin IV over 30 minutes Q3W and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Lumpectomy; Procedure: Mastectomy; Drug: Paclitaxel
Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)ExperimentalPatients receive atezolizumab IV over 30-60 minutes and carboplatin IV over 30 minutes Q3W, and paclitaxel IV over 1 hour QW. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo the collection of blood samples throughout the trial.
Receives: Drug: Atezolizumab; Drug: Carboplatin; Procedure: Lumpectomy; Procedure: Mastectomy; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Tumor Infiltrating Lymphocyte (TIL) Percentage

    Will be measured by histopathologic assay. The TIL percentage after initiation of therapy will be compared between patients receiving neoadjuvant chemotherapy alone (Arm A), and patients receiving neoadjuvant chemotherapy in combination with atezolizumab (Arm B). The post-treatment TIL percentages between two arms will be summarized using descriptive statistics at each time point.

    Measured: Baseline and between days 18-22 following completion of cycle 1 (each cycle is 3 weeks)

  2. Pathologic Complete Response (pCR) Rate

    • Pathologic complete response rates will be summarized using contingency tables and compared using Fisher's exact test between patients receiving neoadjuvant chemotherapy alone (Arm A), and patients receiving neoadjuvant chemotherapy in combination with atezolizumab (Arm B).
    • A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.

    Measured: At the time of surgery (3-6 weeks after last dose of neoadjuvant chemotherapy, neoadjuvant chemotherapy will be up to 12 weeks in length)

Secondary outcomes (1)
  1. Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant

    Adverse events were classified and graded using CTCAE version 5.

    Measured: From start of treatment of through completion of AE follow-up (median length of follow-up 2.98 months, full range 0.26-6.56 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2016 (estimated)
  2. Study start2 Aug 2017
  3. Primary completion18 Dec 2019
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02883062
Sponsor's protocol ID
NCI-2016-01301
Other IDs
NCI-2016-01301, 201706104, 10013, 10013, UM1CA186689, UM1CA186704
Status last verified
Sep 2026
First submitted
29 Aug 2016
Last updated
30 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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