This is a multicenter, national, nonrandomized, phase II trial in subjects with nonsquamous NSCLC patients that have untreated asymptomatic BM. A pre-screening period using brain MRI for patients diagnosed with advanced non-squamous NSCLC EGFR/ALK wild type and ECOG PS 0-1 will be crucial to identify patients with asyntomatic BM. Forty patients will be recruited.
Atezolizumab will be administered intravenously (iv) at a dose of 1200 mg over 60 minutes on day 1 of each cycle. The subsequent cycles of atezolizumab can be administered over 30 minutes, if there were no infusion-related toxicities. Pemetrexed will be administered at a dose of 500 mg/m2 iv over 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4mg bid will be administered one day before and after pemetrexed treatment. Carboplatin will be administered at a dose with an area under the curve of 5 over 30 minutes on day 1 of each cycle approximately 30 minutes after the end of the pemetrexed infusion. After completing 4 to 6 cycles of carboplatin plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab until unacceptable toxicity, disease progression, patient/physician decision or completion of 2 years of therapy. Tumor measurements by CT scan (systemic response) and brain MRI (intracranial response) will be performed every 6 weeks until the 12th week and thereafter every 9 weeks until disease progression. In case of brain progression, rescue with brain radiotherapy should be considered. In case of exclusive brain progression, patients are allowed to receive brain radiotherapy (WBRT or SRS) and then continue with study therapy if the patients maintain clinical benefit and appropriate performance status (ECOG PS≤2).Immunotherapy should be started no later than 4 weeks after completing radiation therapy (brain radiotherapy 2 weeks + 4 weeks of recovery from potential acute toxicity). In case of systemic progression without brain progression, a novel line of systemic treatment should be considered. Patients experiencing systemic progression and/or brain progression will be followed and two post-progression visits will be performed at 30 and 90 days. Response will be assessed independently in the brain and systemically: systemic response will be evaluated according to RECIST v1.1 and brain response according to the RANO response assessment criteria for BM (RANO-BM). Adverse events will be assessed throughout and assessed using the CTCAE version 4.03. EORTC quality of life questionnaire EORTC C30 and the submodules QLQ-LC13 and BN20 will be assessed in the ITT population at baseline, cycle 5 (week 12),cycle 9 (week 24), at end of study treatment (30 and 90 days) and/or at disease progression. Periodic evaluations of the trial data will be conducted by an independent DMC to ensure subject safety and to evaluate the efficacy at the interim analyses. Neurocognitive assessment including the standardized neuropsychological tests: Hopkins Verbal Learning Test (HVLT), Trail Making Test (TMT), Rey-Osterrieth complex figure test (ROCF) and Controlled Oral Word Association Test (COWA) will be assessed at baseline cycle 5 (week 12),cycle 9 (week 24), at end of study treatment (30 and 90 days) and/or at disease progression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
* Induction (four or six 21-day cycles) : Atezolizumab 1200 mg / iv + carboplatin 5 AUCs + pemetrexed 500 mg/m2 * Maintenance (21-day cycles): atezolizumab 1200 mg/iv + pemetrexed 500 mg/m2.
Hospital General Universitario de Elche
Elche, Alicante, Spain
Hospital Universitari Germans Tries i Pujol
Badalona, Barcelona, Spain
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, Spain
Efficacy of Atezolizumab + CBDCA + Pemetrexed by Evaluating PFS Rate
Percentage of subjects without disease progression (intracranial or systemic) at 12 weeks after enrollment. Determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively. Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI:Complete Response(CR),Disappearance of all target lesions; Partial Response (PR) ≥30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) ≥20% increase in the sum of diameters of target lesions. Reponse Evaluation criteria in brain metastasis (RANO) for target lesions assessed by MRI: Complete Response (CR) Disappearance of all CNS target lesions without use of corticosteroids, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions;Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions
Time frame: 12 weeks after enrollment
Efficacy of Atezolizumab + CBDCA + Pemetrexed by Measuring Objective Response.
Objective response defined as a complete response or partial response on two consecutive evaluations 6 weeks apart, as determined by the investigator according to RANO and RECIST v1.1 criteria for brain and systemic disease respectively. Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for target lesions and assessed by MRI: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR) ≥30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) ≥20% increase in the sum of diameters of target lesions. Reponse Evaluation criteria in brain metastasis (RANO) for target lesions assessed by MRI: Complete Response (CR), Disappearance of all CNS target lesions without use of corticosteroids, Partial response (PR) ≥30% decrease in the sum longest diameter of CNS target lesions; Progessive disease (PD) ≥20% increase in the sum longest diameter of CNS target lesions or the appearance of new lesions
Time frame: Two consecutive evaluations 6 weeks apart
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Complejo Hospitalario de la Coruña
A Coruña, Coruña, Spain
Hospital Insular de Gran Canaria
Las Palmas de Gran Canaria, Las Palmas, Spain
Complexo Hospitalario Universitario de Vigo
Vigo, Pontevedra, Spain
Hospital General de Alicante
Alicante, Spain
H.U.Vall D´Hebrón
Barcelona, Spain
Hospital de Santa Creu i Sant Pau
Barcelona, Spain
Hospital Dr. Josep Trueta
Girona, Spain
...and 5 more locations