Atezolizumab in Combination With Carboplatin Plus Pemetrexed in Chemotherapy-naïve Patients With Asymptomatic Brain Metastasis (ATEZO-BRAIN)
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|ClinicalTrials.gov Identifier: NCT03526900|
Recruitment Status : Active, not recruiting
First Posted : May 16, 2018
Last Update Posted : May 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer Stage IV||Drug: Atezolizumab||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Non-randomized Study of a Atezolizumab (MPDL3280A) in Combination With Carboplatin Plus Pemetrexed in Patients Who Are Chemotherapy-naïve and Have Stage IV Non-squamous Non-small Cell Lung Cancer Twith Asymptomatic Brain Metastasis|
|Actual Study Start Date :||July 7, 2018|
|Actual Primary Completion Date :||March 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Induction phase: atezolizumab will be given intravenously (iv) at a dose of 1200 mg for 60 minutes on day 1 of each cycle. Subsequent atezolizumab cycles may be administered for 30 minutes, if there were no perfusion-related toxicity. Pemetrexed will be administered at a dose of 500 mg/m2 IV for 15 minutes on day 1 of each cycle. In addition, folic acid, vitamin B12, and dexamethasone 4 mg will be given the day before and the day after treatment with pemetrexed. Carboplatin will be given at a dose with an area under the 5 curve for 30 minutes on day 1 of each cycle, approximately 30 minutes after the pemetrexed infusion is complete. After completing 4 to 6 cycles of Carboplatino plus pemetrexed and atezolizumab, patients will continue with pemetrexed in combination with atezolizumab (maintenance phase) until they have an unacceptable toxicity, progression of the disease, decision of the patient/physician or have Completed 2 years of treatment.
Other Name: Tecentriq
- Efficacy of atezolizumab + CBDCA + pemetrexed by evaluating PFS [ Time Frame: 12 weeks after enrollment ]To evaluate the efficacy of Atezolizumab in terms of rate of progression free survival after enrollment defined as the sate of patients free of disease progressionor death from any cause wichever occurs first at 12 weeks as determined by the investigator according to RANO and RECIST v1.1 criteria for brain and Systemix disease respectively.
- Efficacy of atezolizumab + CBDCA + pemetrexed by measuring objective response. [ Time Frame: Two consecutive evaluations 6 weeks apart ]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.
- The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration intro the Response Assessment. [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months. ]The NANO scale (Neuro-Oncology Scale) is and objective clinician-reported outcome of neurologic function with high inter-observer agreement quantifiable evaluation of 9 relevant neurologic domains.The NANO scale evaluates 9 major domains of neurologic function that are most relevant to patients with supratentorial, infratentorial, and brainstem tumors, including gait, strength, upper extremity ataxia, sensation, visual fields, facial strength, language, level of consciousness, and behavior. Each domain is subdivided into 3 or 4 levels of function with scores based on discrete quantifiable measures. Thus, levels of function for each domain range from 0 to 2 or 0 to 3. A score of 0 indicates normal function, while the highest score indicates the most severe level of deficit for that domain.
- Number of patients who have neurological deterioration. [ Time Frame: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months. ]To record the number of patients requiring an increase steroid dose for > 96h to control neurologic symptoms.
- Median time to brain radiotherapy (WBRT or SRS) [ Time Frame: From date of randomization until the date of first needed salvage therapy, assessed up to 48 months. ]Register the median time to needed brain radiotherapy (WBRT or SRS).
- Quality of life measured with Health-related Quality of Life questionnaires (EORTC QLQ-BN20). [ Time Frame: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months. ]QLQ tests allow to capture the patient's' own perception about their physical, mental, and social functions, as well as other related symptoms frequently suffered by cancer patients specially in patients with brain cancer (EORTC QLQ-BN20).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03526900
|Hospital General Universitario de Elche|
|Elche, Alicante, Spain, 03203|
|Hospital Universitari Germans Tries i Pujol|
|Badalona, Barcelona, Spain, 08916|
|Hospital Universitari de Bellvitge|
|L'Hospitalet de Llobregat, Barcelona, Spain, 08908|
|Complejo Hospitalario de la Coruña|
|La Coruña, Coruña, Spain, 15006|
|Hospital Insular de Gran Canaria|
|Las Palmas de Gran Canaria, Las Palmas, Spain|
|Complexo Hospitalario Universitario de Vigo|
|Vigo, Pontevedra, Spain, 36036|
|Hospital General de Alicante|
|Alicante, Spain, 03010|
|Barcelona, Spain, 08035|
|Hospital de Santa Creu i Sant Pau|
|Barcelona, Spain, 08041|
|Hospital Dr. Josep Trueta|
|Girona, Spain, 17007|
|Hospital Fundación Jiménez Díaz|
|Madrid, Spain, 28040|
|H. La Paz|
|Hospital General Universitario de Valencia|
|Valencia, Spain, 46014|
|Hospital La Fe|
|Valencia, Spain, 46026|
|Hospital Clínico Universitario de Valladolid|
|Valladolid, Spain, 47003|
|Principal Investigator:||Ernest Nadal, MD||Hospital Universitari de Bellvitge|