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

NCT02883062 | Active Not Recruiting Phase 2 Results FDA Drug

• 5 other identifiers: NCI-2016-0130120170610410013UM1CA186689UM1CA186704
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 14

Brief 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. 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.

Conditions

Invasive Breast Carcinoma; Stage II Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma; Stage III Breast Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

  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)

• Safety of the Treatment Regimen as Measured by the Number of Grade 3 or 4 Adverse Events Experienced by Participant

  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)

Other Outcomes (6)

• Incidence of Potential Biomarkers of Response

  Up to the time of surgery

• Change in Immune Response by Immune Signature

  Up to the time of surgery

• Change in Immune Response PD-L1 Expression

  Up to the time of surgery

Study Arms (2)

Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)

ACTIVE COMPARATOR

Patients 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.

Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Lumpectomy; Procedure: Mastectomy; Drug: Paclitaxel

Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)

EXPERIMENTAL

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. Patients also undergo the collection of blood samples throughout the trial.

Drug: Atezolizumab; Drug: Carboplatin; Procedure: Lumpectomy; Procedure: Mastectomy; Drug: Paclitaxel

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy); Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)

Lumpectomy PROCEDURE

Undergo lumpectomy

Also known as: Lumpectomy of Breast, Partial Mastectomy

Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy); Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)

Mastectomy PROCEDURE

Undergo mastectomy

Also known as: Mammectomy

Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy); Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy); Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

atezolizumab; Specimen Handling; Carboplatin; Mastectomy, Segmental; Mastectomy; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Coordination Complexes; Organic Chemicals; Surgical Procedures, Operative; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Dr. William Gillanders
• Organization: Washington University School of Medicine

gillandersw@wustl.edu

314-747-0072

Study Officials

• William E Gillanders

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2016
• First Posted: August 30, 2016
• Study Start: August 2, 2017
• Primary Completion: December 18, 2019
• Study Completion (Estimated): September 11, 2026
• Last Updated: April 13, 2026
• Results First Posted: June 18, 2024

Record last verified: 2026-03

Locations

US (14)