Atezolizumab After Concurrent Chemo-radiotherapy Versus Chemo-radiotherapy Alone in Limited Disease Small-cell Lung Cancer

Small-cell Lung Cancer Clinical Trial

— ACHILES  

Official title:

A Randomized Phase II Study Comparing Atezolizumab After Concurrent Chemo-radiotherapy With Chemo-radiotherapy Alone in Limited Disease Small-cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03540420
• Other study ID #: 2017-11-03BHG
• Secondary ID: 2017-004572-62
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 31, 2018
• Est. completion date: April 2027

Study information

• Verified date: January 2024
• Source: Norwegian University of Science and Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Some patients with limited disease small-cell lung cancer (LD SCLC) are cured after chemo-radiotherapy, but the majority relapse and die from their cancer. Better therapy is needed. Immunotherapy represents the largest advance in cancer therapy in recent years and has demonstrated promising activity in SCLC. In this study we will investigate whether atezolizumab prolongs survival in LD SCLC patients who have undergone chemo-radiotherapy.

Description:

Patients who have - completed 4 course of platinum/etoposide and thoracic radiotherapy of 45 Gy/30 fractions, 2 fractions per day - non-progression after chemo-radiotherapy - ECOG performance status 0-2 will be randomized to receive atezolizumab 1200 mg IV every 3 weeks in 12 months or standard of care (observation).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 212
• Est. completion date: April 2027
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed small-cell lung cancer
• Previous radiotherapy to the thorax is allowed as long as the patient can receive TRT of 45 Gy.
• Stage I-III according to TNM v8 ineligible for surgery provided all lesions can be included in a tolerable radiotherapy field ("limited disease")
• ECOG performance status 0-2
• Measureable disease according to the RECIST 1.1
• Adequate organ function defined as: (a) Serum alanine transaminase (ALT) = 2.5 x upper limit of normal (ULN); (b) Total serum bilirubin = 1.5 x ULN; (c)Absolute neutrophil count (ANC) = 1.5 x 10 superscr 9/L; (d) Platelets = 100 x 10 superscr 9/L ; (e) Creatinine < 100 µmol/L and calculated creatinine-clearance > 50 ml/min. If calculated creatinine-clearance is < 50 ml/min, an EDTA clearance should be performed
• No malignant cells in pericardial or pleural fluid (at least 1 sample should be obtained if pleural fluid is present) If there is so little fluid that it cannot easily be collected, the patient is considered eligible.
• Pulmonary function: FEV1 > 1 l or > 30 % of predicted value and DLCO > 30 % of predicted value
• Female patients of childbearing potential (Postmenarcheal, not postmenopausal (>12 continuous months of amenorrhea with no identified cause other than menopause), and no surgical sterilization) should use highly effective contraception and take active measures to avoid pregnancy while undergoing atezolizumab treatment and for at least 5 months after the last dose. Birth control methods considered to be highly effective are listed in Appendix D of the protocol
• Written informed consent

Exclusion Criteria:

• previous systemic therapy for SCLC or immune checkpoint blockade therapy
• serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) which in the opinion of the investigator would compromise the patient's ability to complete the study, or would interfere with the evaluation of the efficacy and safety of the study treatment
• lung disease requiring systemic steroids in doses of >10 mg prednisolone (or equivalent dose of other steroid)
• previous allogeneic or organ transplant
• active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
• history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• live vaccine administered in the last 30 days
• active infection requiring IV antibiotics
• active viral hepatitis or HIV-positive
• conditions - medical, social, psychological - which could prevent adequate information and follow-up
• clinically active cancer other than SCLC with the exception of malignancies with a negligible risk of metastases or death (e.g. 5-years OS rate of >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer. Hormonal therapy for non-metastatic prostate or breast cancer is allowed.
• pregnant or lactating women

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer

Intervention

Drug:
• Atezolizumab
atezolizumab 1200 mg intravenous every 3 weeks in 12 months

Locations

Country	Name	City	State
Denmark	Aalborg Universitetshospital	Aalborg
Denmark	Rigshospitalet	København
Denmark	Odense University Hospital	Odense
Lithuania	National Cancer Institute	Vilnius
Netherlands	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Rijnstate Ziekenhuis	Arnhem
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Medische Centrum Twente	Enschede
Netherlands	Erasmus MC	Rotterdam
Netherlands	Zuyderland Ziekenhuis	Sittard
Netherlands	Antonius Ziekenhuis	Utrecht
Netherlands	Isala Ziekenhuis	Zwolle
Norway	Ålesund Hospital	Ålesund
Norway	Haukeland Universitetssykehus	Bergen
Norway	Drammen sykehus - Vestre Viken	Drammen
Norway	Haugesund hospital	Haugesund
Norway	Sørlandet Sykehus	Kristiansand
Norway	Sykehuset i Kristansund	Kristiansund
Norway	Sykehuset Levanger	Levanger
Norway	Molde Sjukehus	Molde
Norway	Akershus Universitetssykehus AHUS	Oslo
Norway	Oslo University Hospital Ullevål	Oslo
Norway	Stavanger University Hospital	Stavanger
Norway	Universitetssykehuset Nord-Norge	Tromsø
Norway	Cancer Clinic at St. Olavs Hospital	Trondheim
Norway	Volda hospital	Volda
Sweden	Gävle hospital	Gävle
Sweden	Sahlgrenska Universitetssjukhus	Göteborg
Sweden	Universitetssjukhuset Linköping	Linköping
Sweden	Skånes University Hospital	Lund
Sweden	Universitetssjukhuset Örebro	Örebro
Sweden	Karolinska University Hospital	Stockholm
Switzerland	Universitätsspital Basel	Basel
Switzerland	Inselspital	Bern
Switzerland	University Hospital Inselspital	Bern
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Kantonsspital Olten - Solothurner Spitäler	Olten
Switzerland	Cantonal Hospital of St. Gallen	St Gallen
Switzerland	Spital STS AG	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Hirslanden Klinik	Zürich

Sponsors (45)

Lead Sponsor

Collaborator

Norwegian University of Science and Technology

Aalborg University Hospital, Alesund Hospital, Amphia Hospital, Cantonal Hospital of St. Gallen, Ente Ospedaliero Cantonale, Bellinzona, Erasmus Medical Center, Freiburger Spital, Gävle Hospital, Haukeland University Hospital, Helse Fonna, Helse Nord-Trøndelag HF, Helse Stavanger HF, Insel Gruppe AG, University Hospital Bern, Isala, Kantonsspital Graubünden, Kantonsspital Olten, Kantonsspital Winterthur KSW, Karolinska University Hospital, Klinik Hirslanden, Zurich, Kristiansund Hospital, Medisch Spectrum Twente, Molde Hospital, National Cancer Institute, Lithuania, Nordlandssykehuset HF, Odense University Hospital, Ôrebro University Hospital, Oslo University Hospital, Rigshospitalet, Denmark, Rijnstate Hospital, Sahlgrenska University Hospital, Sweden, Skane University Hospital, Sorlandet Hospital HF, Spital STS AG, St. Antonius Hospital, St. Olavs Hospital, The Netherlands Cancer Institute, Ullevaal University Hospital, University Hospital of North Norway, University Hospital, Akershus, University Hospital, Basel, Switzerland, University Hospital, Linkoeping, Vestre Viken Hospital Trust, Volda Hospital, Zuyderland Medisch Centrum

Countries where clinical trial is conducted

Denmark,  Lithuania,  Netherlands,  Norway,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2 year survival		2 year after enrollment is completed
Secondary	Progression free survival		2 year after enrollment is completed
Secondary	Best response rate during study treatment period		2 year after enrollment is completed
Secondary	Number of treatment-related adverse events as assessed by CTCAE v5.0	The number of mild (grade 1-2), severe (grade 3-4) and fatal (grade 5) events during the chemoradiotherapy will be reported for the whole study cohort.	13 months after last patient completed atezolizumab therapy
Secondary	Patient-reported Health related quality of life on the EORTC QLQ-C30 and LC13 questionnaires.	Patients will report HRQoL before and after chemoradiotherapy and then at each evaluation the first 2 years. Mean scores will be compared at each timepoint. A difference of 10 points or more is considered clinically relevant.	2 year after enrollment is completed