Study to assess efficacy of Atezolizumab in combination with Carboplatin Plus Pemetrexed in patients who are chemotherapy-naïve and have stage IV non-squamous non-small cell lung cancer with asymptomatic brain metastases (ATEZO-BRAIN)
- Conditions
- Atezolizumab combined with carboplatin and pemetrexedMedDRA version: 20.0Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-005154-11-ES
- Lead Sponsor
- Spanish Lung Cancer Group (SLCG/GECP)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
Patients must meet the following criteria for study entry:
- Signed Informed Consent Form
- Age = 18 years at time of signing Informed Consent Form
- Ability to comply with the study protocol, in the investigator’s judgment
- ECOG Performance Status (PS) of 0 to 1
- Histologically or cytologically confirmed, Stage IV non-squamous NSCLC; patients with mixed non-small cell histology (i.e. squamous and non-squamous) are eligible whether the major component appears to be non-squamous
- No prior treatment or Stage IV non-squamous NSCLC: Patients with a sensitizing mutation in EGFR gene are excluded given that EGFR TKIs are the appropriate front-line treatment for those patients, patients with an ALK fusion are excluded given that ALK TKIs are the appropriate front-line treatment for those patients, patients with unknown EGFR and ALK status require test results at screening, they can be assessed at a local or central laboratory
- Patients who received prior neo-adjuvant, adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months since the last dose of chemotherapy and/or radiotherapy
- Asymptomatic untreated brain metastases
- Steroids treatment (dexamethasone) is allowed and patients that remained asymptomatic for 2 weeks on steroids will be eligible when they were receiving = 4mg dexamethasone once a day
- Systemic measurable disease by computed tomography (CT) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria AND brain measurable disease by magnetic resonance imaging (MRI) per RANO-BM criteria (at least two measurable lesions =10mm, see Appendix 3)
- Availability of a formalin-fixed paraffin-embedded block containing tumor tissue or 5 unstained slides
- Adequate hematopoietic, hepatic and renal function: ANC = 1,500 cells/µL, Lymphocyte count = 500 cells/µL, Platelet count = 100,000 cells µL, Hemoglobin = 9.0 g/dL (transfusion are allowed), INR or aPTT = 1.5 x upper limit of normal (ULN); patients receiving therapeutic anticoagulation should be on a stable dose, ALT, AST and/or alkaline phosphatase = 2.5 x ULN, with the following exceptions: -patients with known liver metastasis: ALT and/or AST = 5 x ULN, -patients with known bone metastasis: alkaline phosphatase = 5 x ULN, Serum bilirubin = 1.5 x ULN; patients with known Gilbert disease who have serum bilirubin = 3 x ULN may be recruited), Calculated creatinine clearance (CRCL) = 45 mL/min (based on the standard Cockcroft and Gault formula)
- For women of childbearing potential: agreement to remain abstinent or use contraceptive non-hormonal methods with a failure rate of < 1% per year during the treatment period and for 3 months after the last dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization and copper intrauterine devices
- For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm. With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period
Patients who meet any of the following criteria will be excluded from study entry:
- History of other malignancy within 3 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
- Patients harboring an EGFR mutation or an ALK fusion will be excluded
- Leptomeningeal carcinomatosis or metastases in the brain stem, mid-brain, pons, medulla or lesions causing obstructive hydrocephalus
- Patients with neurological symptoms, including those receiving > 4mg of dexamethasone will not be eligible for this study
- Single exclusive brain metastasis amenable to surgical treatment or radiosurgery in patients not having metastasis in other organ
- Spinal hemorrhagic metastases will be excluded
- Prior surgical resection of brain or spinal lesions in the prior 28 days
- Previous systemic treatment or neo-adjuvant or adjuvant chemotherapy less than 6 months before enrollment
- Clinical significant comorbidities that impaired administration of platinum-based chemotherapy
- History of autoimmune disease, including but not limited to myasthenia gravis, myosistis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis: patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone are eligible for this study, patients with controlled Type 1 diabetes mellitus on a stable dose of insulin are eligible for this study, patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriasic arthritis would be excluded) are permitted provided that they meet the following conditions: rash covers less than 10% of body surface area, disease is well controlled at baseline and only requires low-potency topical steroids, no acute exacerbations during the last 12 months
- History of idiopathic pulmonary fibrosis, drug-induced pneumonitis or active radiation pneumonitis out of the radiation field
- Previous treatment with immune checkpoint inhibitors or CD137 and OX-40 agonists
- Treatment with investigational therapy within 28 days prior to initiation of study drug
- Positive for hepatitis C virus (HCV) antibody or for hepatitis B surface antigen (HBsAg) at screening. Patients with past or resolved hepatitis B virus (HBV) infection (HBcAb positive with absence of HBsAg) would be eligible whether they are negative for HBV DNA. Patients positive for HCV antibody would be eligible whether they are negative for HCV RNA
- Active tuberculosis or known HIV infection
- Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator’s judgment
- Serious infection requiring oral or IV antibiotics within 14 days prior to screening
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method