Atezolizumab Plus Induction Chemotherapy Plus CT-radiotherapy. (APOLO)

NCT04776447 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: GECP 20/08_APOLO2020-004459-33
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 22

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

Conditions

Lung Diseases; Carcinoma, Non-Small-Cell Lung; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Respiratory Tract Neoplasms; Carcinoma Bronchiogenic Stage III; Thoracic Neoplasms

Keywords

Chemo-radiotherapy; Immunotherapy; Atezolizumab; Carboplatin; Paclitaxel; Induction chemotherapy; Maintenance treatment; ctDNA levels; Antineoplastic Agents; Induction chemo-immunotherapy; Non-resectable non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS) at 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.

  From the date of the end of treatment until 12 months

Secondary Outcomes (4)

• 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

• 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

• 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

Study Arms (1)

Experimental: Atezolizumab plus induction chemotherapy plus CT-radiotherapy

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Placlitaxel; Drug: Atezolizumab

Interventions

Carboplatin DRUG

Structure: The cis-diamino (cyclobutane-1, 1 dicarboxylate) plating. Stability: 24 hours at ambient temperature in 5% glucose, glucosamine or physiologic saline. It is recommended not to dilute with chlorinated solutions for this could affect the carboplatin. Route of administration: Intravenous infusion. Guidelines of Carboplatin administration: According to the standard of each center. Other Name: ATC code: L01XA02

Also known as: Carboplatinum

Experimental: Atezolizumab plus induction chemotherapy plus CT-radiotherapy

Placlitaxel DRUG

Structure: A diterpene whose composition is: 5b, 20-epoxy-1, 2a, 4,7b, 10b, 13a-hexahidroxytax-11-en 9 one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)- N-benzoyl-3-phenylisoserine. Stability: Concentrations of 0.3-1.2 mg/ml in 5% dextrose or normal saline have demonstrated chemical and physical stability for more than 27 hours at ambient temperature (25ºC approximately). The intact vial must be stored between 15º and 25ºC. Guidelines of Paclitaxel administration: Paclitaxel must be administered by infusion over 3 hours in dextrose (D5W) or normal saline (NS). The concentration must not exceed 1.2 mg/ml.

Also known as: Taxol

Experimental: Atezolizumab plus induction chemotherapy plus CT-radiotherapy

Atezolizumab DRUG

Atezolizumab is a humanized immunoglobulin (IgG1) monoclonal antibody that is produced in Chinese hamster ovary (CHO) cells. Atezolizumab targets programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (ICs) or tumor cells (TCs) and prevents interaction with the programmed death-1 (PD-1) receptor and B7.1 (CD80), both of which function as inhibitory receptors expressed on T cells and other immune cells. Patients will receive 1200 mg of atezolizumab administered by IV infusion every 21 days (+/- 3 days) in a monitored setting where there is immediate access to trained personnel and adequate equipment/medicine to manage potentially serious reactions.

Also known as: Tecentriq

Experimental: Atezolizumab plus induction chemotherapy plus CT-radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged ≥ 18 years old and ≤ 75 years.
• ECOG Scale (Eastern Cooperative Oncology Group) of performance status of 0 or 1.
• 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 v1.1.
• 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.
• Lymphocyte count ≥ 500/μL.
• Platelet count ≥ 100,000/μL without transfusion.
• Haemoglobin ≥ 10.0 g/dL. Patients may be transfused to meet this criterion.
• INR or aPTT ≤ 1.5 × upper limit of normal (ULN). This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
• AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions:

You may not qualify if:

• 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.
• Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C.
• Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of HBsAg) are eligible only if they are negative for HBV DNA (vaccinated patients are excluded).
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
• Active tuberculosis.
• Symptomatic neuropathy (sensory) grade \> 1 according to the NCI Common Toxicity Criteria for Adverse Events v5.0

Sponsors & Collaborators

• Fundación GECP: lead

Study Sites (22)

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

Location

ICO Badalona, Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Insular de Gran canaria

Las Palmas de Gran Canaria, Gran Canaria, 35016, Spain

Location

Hospitalario Universitario A Coruña

A Coruña, La Coruña, 15006, Spain

Location

Hospital Universitario Severo Ochoa

Leganés, Madrid, 28911, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Parc Taulí

Barcelona, 08208, Spain

Location

Hospital de Basurto

Bilbao, 48013, Spain

Location

ICO Girona, Hospital Josep Trueta

Girona, 17007, Spain

Location

Hospital Universitario de Jaén

Jaén, 23007, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, 28031, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Santa María Nai

Ourense, 32005, Spain

Location

Hospital Son Espases

Palma de Mallorca, 07120, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, 47003, Spain

Location

Related Links

• Web page of the sponsor where users can find more information about Fundación GECP studies

MeSH Terms

Conditions

Lung Diseases; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Carcinoma, Bronchogenic; Thoracic Neoplasms

Interventions

Carboplatin; Paclitaxel; atezolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Bronchial Neoplasms; Lung Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Mariano Provencio, MD

  Fundación GECP President

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Design: Open-label, non-randomized, phase II multi-centre controlled clinical trial.

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 1, 2021
• Study Start: June 16, 2021
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (22)