Clinical Trials /

Neoadjuvant MPDL3280A, Nab-paclitaxel and Carboplatin (MAC) in NSCLC

NCT02716038

Description:

This is a research study to test the effectiveness of nab-paclitaxel + carboplatin + MPDL3280A for treatment of non-small-cell lung carcinoma (NSCLC), which is a type of lung cancer. The study aims to determine if chemotherapy combined with immune-based therapy can lead to improvement in tumor response rates over historical response rates with chemotherapy alone.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant MPDL3280A, Nab-paclitaxel and Carboplatin (MAC) in NSCLC
  • Official Title: A Single-arm, Phase II Study of Neoadjuvant MPDL3280A, Nab-paclitaxel and Carboplatin (MAC) in Resectable Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: AAAQ3153
  • NCT ID: NCT02716038

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
MPDL3280AAtezolizumab, RG7446MPDL3280A, Carboplatin, Nab-paclitaxel
CarboplatinParaplatin, Paraplatin-Aqueous (AQ)MPDL3280A, Carboplatin, Nab-paclitaxel
Nab-paclitaxelAbraxaneMPDL3280A, Carboplatin, Nab-paclitaxel

Purpose

This is a research study to test the effectiveness of nab-paclitaxel + carboplatin + MPDL3280A for treatment of non-small-cell lung carcinoma (NSCLC), which is a type of lung cancer. The study aims to determine if chemotherapy combined with immune-based therapy can lead to improvement in tumor response rates over historical response rates with chemotherapy alone.

Detailed Description

      Lung cancer is the most common cancer in both men and women worldwide, accounting for 13% of
      incident cancers. In 2015, it was estimated there would be 221,200 new lung cancers diagnosed
      in the United States, with 158,040 lung cancer deaths. Approximately 85% of all lung cancers
      are characterized as non-small cell lung cancer (NSCLC).

      Repeated studies have shown neoadjuvant cytotoxic chemotherapy to be safe prior to surgical
      resection of NSCLC with no difference in extent of surgical procedures performed, operative
      morbidity and mortality. The debate remains as to whether neoadjuvant or adjuvant
      chemotherapy is the best approach, with advantages and disadvantages to each.

      The investigators propose that new therapies such as immune checkpoint inhibitors that
      demonstrate promising clinical activity in the advanced disease setting must be incorporated
      into the neoadjuvant setting, in order to maximize benefit early in a patient's treatment
      course, and with a suitable surrogate endpoint that can be used to establish a preliminary
      efficacy signal, prior to initiation of a large confirmatory study.
    

Trial Arms

NameTypeDescriptionInterventions
MPDL3280A, Carboplatin, Nab-paclitaxelExperimentalSubjects with advanced or recurrent cancers receiving: MPDL3280A every 21 days for up to 84 days Carboplatin every 21 days for up to 84 days Nab-paclitaxel every 7 days for up to 84 days
  • MPDL3280A
  • Carboplatin
  • Nab-paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have pathologically confirmed non-small cell lung cancer, of either
             squamous or non-squamous histology.

          -  Stage 1B-3A

          -  Deemed surgically resectable by a thoracic surgeon

          -  Age ≥ 18 years

          -  Radiologically measurable disease, as defined by response evaluation criteria in solid
             tumours (RECIST) v1.1

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Females of child-bearing potential must:

               -  Either commit to true abstinence from heterosexual contact, 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.

               -  Have a negative serum pregnancy test (β -hCG) result at screening and agree to
                  ongoing pregnancy testing during the course of the study, and after the end of
                  study therapy.

          -  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.

               -  Patients who do not have tissue specimens meeting eligibility requirements may
                  undergo a biopsy during the screening period.

          -  Adequate organ and marrow function as defined below:

               -  Lymphocyte count ≥300/microliter (mcL)

               -  Neutrophil count ≥1,500/mcL

               -  Hemoglobin ≥9.0g/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)(SGOT)/alanine aminotransferase (ALT)(SGPT) ≤2.5
                  × 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 m2 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 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 HIV infection.

               -  Patients with past or resolved hepatitis B infection (defined as having a
                  negative hepatitis B surface antigen (HBsAg) test and a positive for the antibody
                  test to detect antibodies to hepatitis B core antigen (anti-HBc) are eligible.

               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if
                  polymerase chain reaction (PCR) is negative for HCV RNA.

          -  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, Sjögren's
             syndrome, Bell's palsy, Guillain-Barré 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 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

                    -  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 oral or
             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 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

          -  History of interstitial lung disease or pneumonitis of any cause

        Immunotherapy-Related Exclusion Criteria:

          -  Prior treatment with anti-PD-1, anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen
             (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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with major pathologic response (MPR)
Time Frame:84 days
Safety Issue:
Description:Major pathologic response rate (MPR) is defined as > 90% decrease in viable tumor.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Columbia University

Trial Keywords

  • Non-Small Cell Lung Cancer
  • Non-Small-Cell Lung Carcinoma
  • Nonsmall Cell Lung Cancer
  • NSCLC

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