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

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ClinicalTrials.gov Identifier: NCT03540420

Recruitment Status : Active, not recruiting

First Posted : May 30, 2018

Last Update Posted : May 6, 2023

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

University Hospital of North Norway

Alesund Hospital

Vestre Viken Hospital Trust

University Hospital, Akershus

Helse Nord-Trøndelag HF

Helse Stavanger HF

Haukeland University Hospital

Sorlandet Hospital HF

Ullevaal University Hospital

Molde Hospital

Helse Fonna

Nordlandssykehuset HF

Volda Hospital

Kristiansund Hospital

Sahlgrenska University Hospital, Sweden

Skane University Hospital

Karolinska University Hospital

Ôrebro University Hospital

Gävle Hospital

University Hospital, Linkoeping

Odense University Hospital

Aalborg University Hospital

Rigshospitalet, Denmark

National Cancer Institute, Lithuania

Kantonsspital Winterthur KSW

University Hospital, Basel, Switzerland

University Hospital Inselspital, Berne

Kantonsspital Graubünden

Freiburger Spital

Klinik Hirslanden, Zurich

Kantonsspital Olten

Spital STS AG

Ente Ospedaliero Cantonale, Bellinzona

Cantonal Hospital of St. Gallen

St. Olavs Hospital

Oslo University Hospital

Rijnstate Hospital

Isala

Zuyderland Medisch Centrum

The Netherlands Cancer Institute

St. Antonius Hospital

Amphia Hospital

Medisch Spectrum Twente

Erasmus Medical Center

Information provided by (Responsible Party):

Norwegian University of Science and Technology

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Small-cell Lung Cancer	Drug: Atezolizumab	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	212 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Randomized Phase II Study Comparing Atezolizumab After Concurrent Chemo-radiotherapy With Chemo-radiotherapy Alone in Limited Disease Small-cell Lung Cancer
Actual Study Start Date :	July 31, 2018
Estimated Primary Completion Date :	December 2023
Estimated Study Completion Date :	December 2026

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Lung cancer

MedlinePlus related topics: Lung Cancer

Drug Information available for: Atezolizumab

Genetic and Rare Diseases Information Center resources: Small Cell Lung Cancer

U.S. FDA Resources

Arms and Interventions

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: anti-PDL1 Tecentriq
No Intervention: Observation standard care after completed chemo-radiotherapy and non-progression

Outcome Measures

Primary Outcome Measures :

2 year survival [ Time Frame: 2 year after enrollment is completed ]

Secondary Outcome Measures :

Progression free survival [ Time Frame: 2 year after enrollment is completed ]
Best response rate during study treatment period [ Time Frame: 2 year after enrollment is completed ]
Number of treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 13 months after last patient completed atezolizumab therapy ]
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.
Patient-reported Health related quality of life on the EORTC QLQ-C30 and LC13 questionnaires. [ Time Frame: 2 year after enrollment is completed ]
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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations