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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Small-cell Lung Cancer
• Intervention / Treatment: Drug: Atezolizumab

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab; atezolizumab after completed chemo-radiotherapy and non-progression	Drug: Atezolizumab; atezolizumab 1200 mg intravenous every 3 weeks in 12 months; Other Names: Tecentriq; anti-PDL1
No Intervention: Observation; standard care after completed chemo-radiotherapy and non-progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2 year survival	2 year after enrollment is completed

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival		2 year after enrollment is completed
Best response rate during study treatment period		2 year after enrollment is completed
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2018
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: May 28, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Atezolizumab; Chemoradiotherapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: 2017-11-03BHG; 2017-004572-62 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No