Atezolizumab, Nab-paclitaxel, and Carboplatin before Surgery in Treating Patients with Stage IB-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

Status: Active

Description

This phase II trial studies the how well atezolizumab, nab-paclitaxel, and carboplatin work before surgery in treating patients with stage IB-IIIA non-small cell lung cancer that can be removed by surgery. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as nab-paclitaxel and carboplatin, 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 atezolizumab, nab-paclitaxel, and carboplatin before surgery may result in additional shrinking of the tumor in patients with non-small cell lung cancer.

Eligibility Criteria

Inclusion Criteria

  • Patients must have pathologically confirmed non-small cell lung cancer, including squamous, non-squamous, mixed histology, or large cell
  • Stage IB-IIIA
  • Deemed potentially surgically resectable by a thoracic surgeon * If the forced expiratory volume in 1 second (FEV1) < 40%, surgical clearance must be obtained from a pulmonologist as well as a thoracic surgeon
  • Radiologically measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Ability to understand and the willingness to sign a written informed consent document
  • Females of child-bearing potential (defined as a sexually mature woman who [1] has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or [2] has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must: * Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception (=< 1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 90 days following treatment completion; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) * Have a negative serum pregnancy test (beta-human chorionic gonadotropin [hCG]) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy; this applies even if the subject practices true abstinence from heterosexual contact
  • Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following treatment discontinuation, even if he has undergone a successful vasectomy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 10 unstained slides, with an associated pathology report, for central testing of tumor PD-L1 expression * Tumor tissue should be of good quality based on total and viable tumor content; fine-needle aspiration, brushing, cell pellet from pleural effusion, and lavage samples are not acceptable; for core-needle biopsy specimens, at least three cores should be submitted for evaluation * Patients who do not have tissue specimens meeting eligibility requirements may undergo a biopsy during the screening period; acceptable samples include core-needle biopsies for deep tumor tissue (minimum of three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions
  • Lymphocyte count >= 300/mcL
  • Neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9.0 g/dl
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) * Patients with Gilbert’s disease: =< 3 x ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN)
  • Alkaline phosphatase =< 2.5 x ULN
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN * Unless the patient is on therapeutic anticoagulation
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 by Cockcroft-Gault estimation

Exclusion Criteria

  • Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 5 years prior to initiation of study treatment; however, the following are allowed: * Hormone-replacement therapy or oral contraceptives * Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)
  • Malignancies other than the disease under study within 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai stage 0, prostate cancer with Gleason score =< 6, and prostate-specific antigen [PSA] =< 10 mg/mL, etc.)
  • Patients who are receiving any other investigational agents concurrently
  • Patients with no smoking history
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MPDL3280A, carboplatin, or paclitaxel
  • Patients with active hepatitis B or C infections or a history of human immunodeficiency virus (HIV) infection
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection including tuberculosis (TB), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • 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)
  • 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 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
  • Patients must not have >= grade 2 pre-existing peripheral neuropathy (per Common Terminology Criteria for Adverse Events [CTCAE])
  • 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
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MPDL3280A
  • History of interstitial lung disease or pneumonitis of any cause
  • IMMUNOTHERAPY-RELATED EXCLUSION CRITERIA:
  • Prior treatment with anti-PD-1, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • 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
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation

Locations & Contacts

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Contact: Justin F. Gainor
Email: JGAINOR@PARTNERS.ORG
Dana-Farber Cancer Institute
Status: Active
Contact: Justin F. Gainor
Email: JGAINOR@PARTNERS.ORG
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Justin F. Gainor
Email: JGAINOR@PARTNERS.ORG

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Catherine Ann Shu
Phone: 212-305-3997
Email: cas2145@cumc.columbia.edu

Tennessee

Nashville
Sarah Cannon Cancer Center
Status: Approved
Contact: David Robert Spigel
Phone: 615-329-7274
Email: dspigel@tnonc.com

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the activity of neoadjuvant atezolizumab (MPDL3280A), nab-paclitaxel, and carboplatin (MAC) in patients with non-small cell lung cancer (NSCLC) as measured by major pathologic response rate (MPR) defined below as > 90% decrease in viable tumor.

SECONDARY OBJECTIVES:

I. To determine the objective response rate, disease free survival, and overall survival of subjects with stage IB-IIIA NSCLC treated with neoadjuvant MAC.

II. To evaluate the safety and feasibility of neoadjuvant MAC in subjects with resectable stage IB-IIIA NSCLC.

III. To detect alterations of tumor immune microenvironment pre-and post-treatment (programmed cell death 1 ligand [PD-L]1, PD-L2, T-cell immunoglobulin and mucin-domain containing-3 [TIM3], lymphocyte-activation gene 3 [LAG3] and T cell subsets [cluster of differentiation (CD)3, CD8, regulatory T cells (Tregs)]).

OUTLINE:

Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1, nab-paclitaxel IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patient then undergo surgical resection of tumor approximately 4 weeks after last dose of study drug.

After completion of study treatment, patients are followed up for 30-90 days and then every 4-6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Catherine Ann Shu

Trial IDs

Primary ID AAAQ3153
Secondary IDs NCI-2016-01097
Clinicaltrials.gov ID NCT02716038