ACHILES Does immunotherapy improve the survival of patients with small cell lung cancer in the Limited Disease stage who have received chemotherapy and radiation therapy?

Denmark, Lithuania, Netherlands, Norway, Sweden, Switzerland (ICTRP)

ICTRP Trial ID
NCT03540420 (ICTRP)

Official title (approved by ethics committee)
ACHILES A randomized phase II study comparing atezolizumab after concurrent chemoradiotherapy with chemoradiotherapy alone in limited disease small-cell lung cancer (BASEC)

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

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

Disease under investigation
Small-cell Lung Cancer (ICTRP)

Intervention under investigation
Drug: Atezolizumab (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 18 Years
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 ?mol/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, Sj?gren syndrome, Guillain-Barr?
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 (ICTRP)

not available

Primary and secondary end points
2 year survival (ICTRP)

Progression free survival;Best response rate during study treatment period;Number of treatment-related adverse events as assessed by CTCAE v5.0;Patient-reported Health related quality of life on the EORTC QLQ-C30 and LC13 questionnaires. (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
University Hospital of North Norway;Alesund Hospital;Vestre Viken Hospital Trust;University Hospital, Akershus;Helse Nord-Tr?ndelag 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;?rebro University Hospital;G?vle Hospital;University Hospital, Linkoeping;Odense University Hospital;Aalborg University Hospital;Rigshospitalet, Denmark;National Cancer Institute, Lithuania;Kantonsspital Winterthur KSW;University Hospital, Basel, Switzerland;Insel Gruppe AG, University Hospital Bern;Kantonsspital Graub?nden;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 (ICTRP)

Additional contacts
Torstein B R?, MD, PhD, Norwegian University of Science and Technology (ICTRP)

Secondary trial IDs
2017-004572-62, 2017-11-03BHG (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT03540420 (ICTRP)