Status and phase
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About
The vast majority of patients with stage I (tumors ≥ 4cm), IIA, IIB (and select stage III) NSCLC are managed with upfront surgery, followed by adjuvant chemotherapy. However, relapse rates remain high and are primarily due to distant, metastatic disease. Previous meta-analysis evaluating the use of neo-adjuvant chemotherapy and adjuvant chemotherapy demonstrate a similar impact on improved disease free survival (DFS) and overall survival (OS). The role of checkpoint inhibitors has been proven to be effective in the treatment of patients with advanced NSCLC, regardless of histology and PD-L1 expression. Results from trials evaluating the use of checkpoint inhibitors alone or in combination with chemotherapy in the neoadjuvant setting for early stage disease are promising. However, there are no trials evaluating the role of concomitant chemotherapy and checkpoint inhibitors in the adjuvant setting. In addition, emerging data supports the use of ctDNA as a promising biomarker for early detection of minimal residual disease and have indicated that the presence of detectable ctDNA after surgery for localized lung cancer is correlated with a 90-100% chance for disease recurrence. Therefore, we propose this current study assessing concomitant chemotherapy plus Atezolizumab in the adjuvant setting for patients with stage I (tumors ≥ 4cm), IIA, IIB (and select stage III) NSCLC who have detectable ctDNA after surgery. The clearance of ctDNA will serve as a surrogate for long term DFS and OS in this patient population.
Enrollment
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Inclusion criteria
Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age >= 18 years at the time of consent.
ECOG Performance Status of 0-1 within 28 days prior to registration.
Patients must have undergone complete surgical resection of their stage I (tumors >= 4cm), IIA, IIB, and select stage III [any T1-3 N1-2 and T4N0-2] NSCLC according to the AJCC 8th edition with negative margins (R0).
Squamous or non-squamous NSCLC histology. Cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus "non-squamous histology".
Surgery for this lung cancer must be completed <= 60 days prior to starting treatment.
Must have tissue available to perform prospective correlative testing. Tissue block is preferred but 10-15 unstained slides (5 μm thick) are also acceptable. If prior PD-L1 results with Dako 22C3 antibody are not available, an additional 5 unstained slides (4 μm thick) must be submitted.
Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.
Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
Contraception method must begin starting from the time of informed consent until 5 months after treatment discontinuation.
For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Exclusion criteria
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 1 week prior to registration.
Has severe hypersensitivity (>= Grade 3) to atezolizumab and/or any of its excipients.
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or infusion proteins.
Has active or history of autoimmune disease or immune deficiency that includes but is not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis.
Known interstitial lung disease that is symptomatic or may interfere with detection or management of suspected drug-related pulmonary toxicity are not permitted.
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g. PleurX) are allowed.
Uncontrolled or symptomatic hypercalcemia (ionized calcium >1.5 mmol/L, calcium >12mg/dL or corrected serum calcium >ULN).
Significant cardiovascular disease within 3 months prior to initiation of study treatment (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident), unstable arrhythmia, or unstable angina.
For patients receiving therapeutic anticoagulation: unstable anticoagulant regimen.
Has a severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
Has a known history of Human Immunodeficiency Virus (HIV). Note: HIV testing is not required.
Has a known history of Hepatitis B or known active Hepatitis C virus infection. Note: If Hepatitis B and Hepatitis C status is unknown, testing is required:
Has a known history of active TB (Bacillus Tuberculosis).
Prior allogeneic stem cell or solid organ transplantation.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 5 months after the last dose of study drug.
Primary purpose
Allocation
Interventional model
Masking
100 participants in 2 patient groups
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Central trial contact
Nasser Hanna, MD; Kimberly Cameron
Data sourced from clinicaltrials.gov
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