Randomized Phase 2 Study of Neoadjuvant Chemotherapy, Carboplatin and Paclitaxel, With or Without Atezolizumab in Triple Negative Breast Cancer (TNBC)
Overview
- Phase
- Phase 2
- Intervention
- Carboplatin
- Conditions
- Invasive Breast Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 67
- Locations
- 27
- Primary Endpoint
- Pathologic Complete Response (pCR) Rate
- Status
- Active, not recruiting
- Last Updated
- 19 days ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. 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: I. To evaluate the safety of the treatment combination of atezolizumab + carboplatin + paclitaxel. EXPLORATORY OBJECTIVES: I. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)
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.
Intervention: Carboplatin
Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)
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.
Intervention: Lumpectomy
Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)
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.
Intervention: Carboplatin
Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)
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.
Intervention: Paclitaxel
Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)
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.
Intervention: Biospecimen Collection
Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)
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.
Intervention: Mastectomy
Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)
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.
Intervention: Lumpectomy
Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)
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.
Intervention: Mastectomy
Arm A (carboplatin, paclitaxel, mastectomy, lumpectomy)
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.
Intervention: Paclitaxel
Arm B (atezolizumab, carboplatin, paclitaxel, breast surgery)
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.
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Pathologic Complete Response (pCR) Rate
Time Frame: At the time of surgery (3-6 weeks after last dose of neoadjuvant chemotherapy, neoadjuvant chemotherapy will be up to 12 weeks in length)
* 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.
Change in Tumor Infiltrating Lymphocyte (TIL) Percentage
Time Frame: Baseline and between days 18-22 following completion of cycle 1 (each cycle is 3 weeks)
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.
Secondary Outcomes
- 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))