A Phase II Trial of Atezolizumab Plus Induction Chemotherapy (CT) Plus Chemo-radiotherapy and Atezolizumab Maintenance Therapy in Non-resectable Stage IIIA-IIIB Non-small Cell Lung Cancer (NSCLC) Patients
Overview
- Phase
- Phase 2
- Intervention
- Carboplatin
- Conditions
- Lung Diseases
- Sponsor
- Fundación GECP
- Enrollment
- 38
- Locations
- 22
- Primary Endpoint
- To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS) at 12 months
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
Open-label, non-randomized, phase II multi-centre controlled clinical trial.
51 non-resectable stage IIIA-IIIB non-small cell lung cancer patients will be enrolled in this trial to evaluate the efficacy of the treatment (Atezolizumab + Induction chemotherapy (CT) + CT-Radiotherapy) in terms of the Progression Free Survival at 12 months
Detailed Description
This is an open-label, non-randomized, phase II multi-centre controlled clinical trial.The total sample size is 51 patients. The population to be included are non-resectable stage IIIA-IIIB non-small cell lung cancer patients. Patients randomised will receive induction treatment (Atezolizumab 1200mg+ Carboplatin AUC5+Paclitaxel 200 mg/m2 for 3 cycles) and concurrent chemotherapy (CT) -radiotherapy treatment for 3 cycles. At the end of concurrent treatment Atezolizumab 1200mg maintenance treatment will start and will be administered for 12 months (16 cycles). The primary objective is to assess the efficacy of the treatment (Atezolizumab + Induction chemotherapy (CT) + CT-Radiotherapy) in terms of the Progression Free Survival (PFS) at 12 months according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. PFS are defined as the time from inclusion until objective tumor progression or death. Patient accrual is expected to be completed within 2 years, treatment is planned to extend during 1.5 years and the patients will be followed up for 2 years. The study will end once survival follow-up has concluded.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, aged ≥ 18 years old and ≤ 75 years.
- •ECOG Scale (Eastern Cooperative Oncology Group) of performance status of 0 or
- •Histologically or cytologically confirmed, non-resectable Stage IIIA-IIIB NSCLC according to the 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology.
- •PET-CT (Positron Emission Tomography -Computed tomography) and brain computed tomography or Magnetic resonance imaging (MRI) at baseline to confirm the absence of distant disease.
- •Mediastinal involvement could be considered without histological confirmation when no margin can be distinguished in the lymph node mass.
- •No prior treatment with anti-neoplastic drugs or thoracic radiotherapy for Stage IIIA-IIIB NSCLC.
- •Patients who have received prior neo-adjuvant, adjuvant chemotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from enrollment since the last chemotherapy.
- •Presence of at least one measurable disease by CT-SCAN, as defined by RECIST v1.
- •Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to enrollment:
- •Neutrophils ≥ 1500 cells/μL without granulocyte colony-stimulating factor support.
Exclusion Criteria
- •Patients with known sensitizing mutation or an amplification in the epidermal growth factor receptor (EGFR) gene, ALK fusion oncogene.
- •Known STK-11 ligand alterations, MDM2 amplifications or ROS1 translocations.
- •Weight loss \>10% within the previous 3 months.
- •Malignant pleural effusion or pericardial effusion: both will be considered as suggestive of metastatic disease. Also excluded those with negative cytology but being exudates.
- •Patients with non-visible by thoracic X-Ray pleural effusion or too small to be safely punctioned could be included.
- •Malignancies other than NSCLC within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 3-year OS \> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated with radiotherapy or surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent).
- •Women who are pregnant, lactating, or intending to become pregnant during the study.
- •Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the Atezolizumab formulation.
- •History of autoimmune disease.
- •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.
Arms & Interventions
Experimental: Atezolizumab plus induction chemotherapy plus CT-radiotherapy
Induction Treatment: Atezolizumab: 1200mg, IV infusion Carboplatin: AUC5, IV infusion Paclitaxel: 200 mg/m2 The treatment will start within 1-5 days from enrollment. The treatment will be 3 cycles administered at 21-day intervals. Concurrent Chemotherapy (CT)-Radiotherapy Treatment: Chemotherapy and radiotherapy treatment will be at the discretion of the principal investigator of each site. It is recommended to use as concurrent chemotherapy treatment a platinum based doublet. After the 3rd cycle of the induction treatment, concurrent treatment will start, 1st concurrent cycle will be administered from day 1 of cycle 3 of induction treatment. Concurrent chest radiotherapy will be administered starting at day 1 of cycle 1 of concurrent chemo-radiotherapy. Maintenance with Atezolizumab: Atezolizumab: 1200mg, IV infusion After the 3rd cycle of the concurrent treatment, Atezolizumab maintenance treatment will start from day 1 of cycle 6 and will be administered for 12 months.
Intervention: Carboplatin
Experimental: Atezolizumab plus induction chemotherapy plus CT-radiotherapy
Induction Treatment: Atezolizumab: 1200mg, IV infusion Carboplatin: AUC5, IV infusion Paclitaxel: 200 mg/m2 The treatment will start within 1-5 days from enrollment. The treatment will be 3 cycles administered at 21-day intervals. Concurrent Chemotherapy (CT)-Radiotherapy Treatment: Chemotherapy and radiotherapy treatment will be at the discretion of the principal investigator of each site. It is recommended to use as concurrent chemotherapy treatment a platinum based doublet. After the 3rd cycle of the induction treatment, concurrent treatment will start, 1st concurrent cycle will be administered from day 1 of cycle 3 of induction treatment. Concurrent chest radiotherapy will be administered starting at day 1 of cycle 1 of concurrent chemo-radiotherapy. Maintenance with Atezolizumab: Atezolizumab: 1200mg, IV infusion After the 3rd cycle of the concurrent treatment, Atezolizumab maintenance treatment will start from day 1 of cycle 6 and will be administered for 12 months.
Intervention: Placlitaxel
Experimental: Atezolizumab plus induction chemotherapy plus CT-radiotherapy
Induction Treatment: Atezolizumab: 1200mg, IV infusion Carboplatin: AUC5, IV infusion Paclitaxel: 200 mg/m2 The treatment will start within 1-5 days from enrollment. The treatment will be 3 cycles administered at 21-day intervals. Concurrent Chemotherapy (CT)-Radiotherapy Treatment: Chemotherapy and radiotherapy treatment will be at the discretion of the principal investigator of each site. It is recommended to use as concurrent chemotherapy treatment a platinum based doublet. After the 3rd cycle of the induction treatment, concurrent treatment will start, 1st concurrent cycle will be administered from day 1 of cycle 3 of induction treatment. Concurrent chest radiotherapy will be administered starting at day 1 of cycle 1 of concurrent chemo-radiotherapy. Maintenance with Atezolizumab: Atezolizumab: 1200mg, IV infusion After the 3rd cycle of the concurrent treatment, Atezolizumab maintenance treatment will start from day 1 of cycle 6 and will be administered for 12 months.
Intervention: Atezolizumab
Outcomes
Primary Outcomes
To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS) at 12 months
Time Frame: From the date of the end of treatment until 12 months
To assess the efficacy of the treatment (Atezolizumab + Induction chemotherapy (CT) + CT-Radiotherapy) in terms of the Progression Free Survival (PFS) at 12 months according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.PFS is defined as the time from inclusion until objective tumor progression or death.
Secondary Outcomes
- To evaluate the Overall survival (OS) rate(From the date of the end of treatment until 12 and 24 months)
- To evaluate the sites of first failure(From the date of the end of treatment until the date of last follow up, assessed up to 36 months)
- To evaluate the Overall Response Rate (ORR) of the treatment(From the date of randomization to the date of last follow up, assessed up to 36 months)
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)(From the subject's written consent to participate in the study through 30 days after the final administration of the drug)