A multicenter Phase III study to assess the efficacy and safety of atezolizumab in combination with chemotherapy in patients with resectable early-stage non-small cell lung cancer (NSCLC)
Zusammenfassung der Studie
The purpose of this study is to compare the positive and negative effects of atezolizumab plus chemotherapy with those of placebo (an inactive substance that looks like atezolizumab) plus chemotherapy in patients with resectable NSCLC (i.e., with removable tumors), to determine which therapy is better suited. In this study, the patient receives either atezolizumab plus chemotherapy or placebo plus chemotherapy before the tumor is surgically removed. This is a multicenter, randomized, double-blind study conducted worldwide. Double-blind means that neither the patient nor the investigator knows which treatment the patient is receiving before the surgery. After the surgical removal of the tumor, the patient's status is unblinded. Randomized means that the assignment of individual patients to a treatment arm is done randomly - like flipping a coin. Depending on which treatment a patient is assigned to, they may receive atezolizumab after surgery for up to 48 weeks. The tests also include examinations using computed tomography (CT) and/or positron emission tomography (PET) as well as magnetic resonance imaging (MRI). Approximately 302 patients will participate in the study.
(BASEC)
Untersuchte Intervention
Atezolizumab is a type of drug known as a PD-L1 antagonist, and a form of cancer immunotherapy that helps the immune system recognize and fight cancer cells. Atezolizumab is approved in several countries for the treatment of advanced urothelial carcinoma, a type of bladder cancer, as well as some types of lung cancer that have spread to other parts of the body and for which surgery is not an option. However, in this study, atezolizumab is being used as an investigational drug. This means that health authorities have not yet approved atezolizumab alone or in combination with chemotherapy for the preoperative treatment of a specific type of tumor that can be surgically removed. Atezolizumab is administered at a fixed dose of 1200 mg. During the study, the patient receives the study treatment every 3 weeks over a period of 12 weeks before surgery. After surgery, the patient receives the study treatment in the first year every 3 weeks or every 6 weeks. Additionally, separate visits for scans are scheduled - in the first year after surgery every 4 months, in years 2 to 5 every 6 months, and after year 5 once a year. Each visit lasts about 1 to 6 hours. If the tumor cannot be completely surgically removed or if some lymph nodes show signs of cancer at the time of surgery, local radiation therapy may be performed to completely remove the tumor. After surgery, the patient continues to receive the study drug (Arm A) or the best supportive care possible (Arm B), until cancer returns or unacceptable side effects occur. After the last dose (Arm A) or the last visit for the best supportive care possible (Arm B), the patient will be followed up approximately every 3 months; this follow-up will continue indefinitely as long as the patient agrees. The total duration of study participation depends on how the patient's cancer responds to treatment.
(BASEC)
Untersuchte Krankheit(en)
Resectable early-stage non-small cell lung cancer (NSCLC).
(BASEC)
- Pathologically documented stage II or IIIA NSCLC or specific form of stage IIIB NSCLC (T3N2 only) with squamous epithelial or non-squamous epithelial histology - Pulmonary function tests must be performed within 6 months of the planned operation and repeated during the pre-examination period if clinically indicated. These should include lung volume measurement, spirometry, and diffusion capacity determination. Abnormal pulmonary function test results can be more accurately assessed by quantitative lung ventilation / perfusion scintigraphy or by ergospirometry - Assessment by the treating surgeon and the involved medical oncologist before enrollment to determine the appropriateness for surgery of the tumor with curative intention (BASEC)
Ausschlusskriterien
NSCLC with non-plate epithelial histology with epidermal growth factor receptor (EGFR) activating mutation or with a fusion oncogene consisting of anaplastic lymphoma kinase (ALK) - Pre-history of malignancy, except for the disease being studied in the study, within 5 years prior to screening. Exceptions are malignancies with a negligible risk of metastasis or death, such as appropriately treated carcinoma in situ of the cervix, non-melanotic skin cancer, localized prostate cancer, ductal carcinoma in situ or uterine cancer stage I - treatment with systemic immunosuppressive drugs (including corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide and TNF-α inhibitors) within 2 weeks before starting study treatment or expected need for systemic immunosuppressive drugs during study treatment (with some exceptions) (BASEC)
Studienstandort
Lausanne, Zürich
(BASEC)
Sponsor
na
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Clinical Trials
+41 61 688 17 58
switzerland.clinical-research@clutterroche.comRoche Pharma (Schweiz) AG
(BASEC)
Allgemeine Auskünfte
Hoffmann-La Roche
(ICTRP)
Wissenschaftliche Auskünfte
Hoffmann-La Roche
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Waadt
(BASEC)
Datum der Bewilligung durch die Ethikkommission
21.08.2018
(BASEC)
ICTRP Studien-ID
NCT03456063 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A PHASE III, DOUBLE-BLINDED, MULTICENTER, RANDOMIZED STUDY EVALUATING THE EFFICACY AND SAFETY OF NEOADJUVANT TREATMENT WITH ATEZOLIZUMAB OR PLACEBO IN COMBINATION WITH PLATINUM-BASED CHEMOTHERAPY IN PATIENTS WITH RESECTABLE STAGE II, IIIA, OR SELECT IIIB NON-SMALL CELL LUNG CANCER (BASEC)
Wissenschaftlicher Titel
A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (ICTRP)
Öffentlicher Titel
A Study of Neoadjuvant Atezolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer (IMpower030) (ICTRP)
Untersuchte Krankheit(en)
Non-Small-Cell Lung (ICTRP)
Untersuchte Intervention
Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyDrug: Placebo ComparatorDrug: Nab-paclitaxelDrug: PemetrexedDrug: CarboplatinDrug: CisplatinDrug: Gemcitabine (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Care Provider). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion criteria: - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Histologically or cytologically confirmed, resectable Stage II, IIIA, or Select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the AJCC/UICC staging system - Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent - Adequate pulmonary and cardiac function to undergo surgical resection - Measurable disease as defined by RECIST v1.1 - Adequate hematologic and end organ function - Negative HIV test at screening - Negative for active HBV and HCV at screening - Adequate tissue for PD-L1 IHC assessmentExclusion criteria: - NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma - Mixed NSCLC and small cell lung cancer histology - Any prior therapy for lung cancer - Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated expected curative outcome - Non-squamous NSCLC histology with activating ALK and EGFR mutation - Pregnant or lactating women - History of autoimmune disease - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or evidence of active of active pneumonitis on screening chest Computed Tomography (CT) scan - Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody - Severe infection within 4 weeks prior to randomization - Significant history of cardiovascular disease (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Independent Review Facility (IRF)-Assessed Event Free Survival (EFS) (ICTRP)
Pathological Complete Response (pCR);Major Pathological Response (MPR);Objective Response (OR);Overall Survival (OS);Investigator-Assessed EFS;Disease-Free Survival (DFS);2-Year and 3-Year OS;2-Year and 3-Year Independent Review Facility-Assessed EFS;2-Year and 3-Year Investigator-Assessed EFS;Change from baseline in HRQoL scores;Percentage of Participants With Adverse Events (AEs);Number and Severity of Surgical Related Adverse Events;Number of Surgical Delays;Length of Surgical Delays;Number of Operative and Post-Operative Complications;Reasons for Surgical Cancellations;Minimum Observed Serum Atezolizumab Concentration (Cmin);Maximum Observed Serum Atezolizumab Concentration (Cmax);Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Clinical Trials, Hoffmann-La Roche (ICTRP)
Sekundäre IDs
2023-504209-35-00, GO40241 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT03456063 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar