Atezolizumab as Induction Therapy in Non-small Cell Lung Cancer

NCT02994576 | Completed Phase 2 DMC

• 2 other identifiers: 2016-000270-382016/2362
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

Based on the efficacy of immunotherapies in advanced disease with a reasonable safety profile/tolerability we could hypothesize that, immunotherapy should work best in the situation of minimal residual disease, Two clinical trials are ongoing to test the role of immunotherapeutic agents in the adjuvant setting: PEARLS trial, a randomized phase III trial with anti-PD1 monoclonal antibody pembrolizumab (MK-3475 or pembrolizumab) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy, and the second randomized phase III trial (NCT02273375) will evaluate the efficacy of an anti-PD-L1 (MEDI 4736) for a maximum of 12 months versus placebo as adjuvant therapy in completed resected stage IB-IIIA NSCLC and completed standard ACT. The role of immunotherapeutic approaches for NSCLC in the neoadjuvant setting is currently unknown. However, based on the survival efficacy of immunotherapeutic strategies in advanced NSCLC where the tumor has not been removed which could produce higher immunogenicity and based on the efficacy of neoadjuvant treatments in NSCLC, we propose to test the safety and efficacy of atezolizumab as neoadjuvant therapy in subjects diagnosed with stage I, II, or IIIA (non N2) NSCLC and who are deemed suitable for surgical resection. Clinical staging of NSCLC is based on computed tomography (CT) of the chest and upper abdomen, brain CT or magnetic resonance imaging and 18F-FDG PETscan to rule out metastatic disease and assess the potential for curative-intent resection. Adjuvant chemotherapy will be performed according the standard clinical guidelines.

Conditions

Nonsmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• The rate of patients without major toxicities or morbidities

  Major toxicities or morbidities: it will include a) treatment toxicity leading to a delay of at least 15 days of the surgery, b) grade ≥ 3 toxicity occurring within 2 months after atezolizumab infusion, c) major postoperative morbidity and d) any death related to the experimental treatment and occurring in the period from the day of injection of atezolizumab to the 30 postoperative days. Patients that did not have surgery because of early progression will be considered as having major toxicities or morbidities.

  During the period defined as the start of treatment and 1 month after the surgery (2-month tolerance rate)

Study Arms (2)

Stage IB(≥ 2 cm)-IIIA non N2, resectable and untreated NSCLC

EXPERIMENTAL

Drug: Atezolizumab

Comparative cohort (patients receiving standard treatment)

NO INTERVENTION

Interventions

Atezolizumab DRUG

Atezolizumab, 1200 mg administered I.V. once

Stage IB(≥ 2 cm)-IIIA non N2, resectable and untreated NSCLC

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histologically documented NSCLC
• Clinical Stage IA (≥ 2 cm)-IIIA non N2 NSCLC eligible for surgical resection
• Initial work-up including pet scan and MRI for staging
• Measurable disease, as defined by RECIST v1.1.
• Apt to surgical resection by a lobectomy or bilobectomy procedure
• ECOG performance status of 0 or 1 (appendix 3)
• Adequate hematologic and organ function, defined by the following laboratory results obtained within 14 days prior to registration:
• White blood cell (WBC) counts \> 2.5 x 10\^9/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (without granulocyte colony-stimulating factor support within 2 weeks prior to Day 1)
• Platelet count ≥100 x 10\^9/L
• Hemoglobin ≥ 9.0 g/dL. Patients may be transfused to meet this criterion.
• AST, ALT, and alkaline phosphatase ≤ 2.5 X the upper limit of normal (ULN),
• Serum bilirubin ≤ 1.5 X ULN. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 X ULN may be enrolled.
• International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN -This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma for at least five years before registration.
• Prior therapy for lung cancer
• Pregnant and breast feeding women
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab product
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, Type I diabetes mellitus, vasculitis, or glomerulonephritis (see Appendix 5 for a more comprehensive list of autoimmune diseases). Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• History of HIV infection
• Patients with active hepatitis B (chronic or acute) or hepatitis C Patients with past/resolved HBV infection (defined as the presence of anti-hepatitis B core antibody, IgG anti-HBs + and absence of HbsAg) are eligible. HBV DNA should be obtained in these patients prior to Day 1.
• Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
• Active tuberculosis
• Severe infections within 4 weeks prior to registration, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Signs or symptoms of infection within 2 weeks prior to registration
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (3)

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

Centre Hospitalier de Chauny

Chauny, France

Location

Centre Marie Lannelongue

Le Plessis-Robinson, France

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

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

Study Record Dates

• First Submitted: December 13, 2016
• First Posted: December 16, 2016
• Study Start: December 12, 2016
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: September 29, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)