A randomized phase II study comparing atezolizumab after concurrent chemoradiotherapy with chemoradiotherapy alone in limited disease small-cell lung cancer

Phase 1

• Conditions: imited disease small-cell lung cancer; MedDRA version: 21.1Level: PTClassification code 10041069Term: Small cell lung cancer limited stageSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004572-62-LT
• Lead Sponsor: orwegian University of Science and Technology, Department of Clinical and molecular medicine

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-16
• Last Update Posted: 28 September 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 212

Inclusion Criteria

1.Histologically or cytologically confirmed small-cell lung cancer
2.No prior systemic therapy for SCLC or immune checkpoint blockade therapy
3.Previous radiotherapy to the thorax is allowed as long as the patient can receive TRT of 45 Gy. If it later turns out that 45 Gy or 60 Gy cannot be administered, the patient should be excluded.
4.Stage I-III according to TNM v8 ineligible for surgery provided all lesions can be included in a tolerable radiotherapy field (limited disease”)
5.Age = 18 years
6.ECOG performance status 0-2
7.Measureable disease according to the RECIST 1.1
8.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 109/L
d.Platelets = 100 x 109/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.
9.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.
10.Pulmonary function: FEV1 > 1 l or > 30 % of predicted value and DLCO > 30 % of predicted value
11.All fertile patients should use safe contraception
12.Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 106
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 106

Exclusion Criteria

11.Any serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) that in the opinion of the investigator would compromise the patient’s ability to complete the study or interfere with the evaluation of the efficacy and safety of the study treatment
12.Any autoimmune or lung disease requiring systemic steroids in doses of >10 mg prednisolone (or equivalent dose of other steroid)
13.Any previous allogeneic or organ transplant
14.Any 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
15.Any 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
16.Any live vaccine last 30 days, active infection requiring IV antibiotics, no active viral hepatitis or HIV-positive
17.Any conditions – medical, social, psychological – which could prevent adequate information and follow-up
18.Any 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.
19.Pregnancy or lactating women

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To investigate whether immunotherapy improves efficacy with respect to best response rates, progression free survival and symptom relief. To compare the frequency and severity of side effects, and patient-reported quality of life. To characterize the patients who benefit the most from the treatment with respect to clinical characteristics, tissue, blood and urine biomarkers.;Main Objective: To investigate whether adjuvant atezolizumab treatment after standard, concurrent chemo-radiotherapy improves survival in limited disease small-cell lung cancer patients - as compared to chemo-radiotherapy alone. ;Primary end point(s): 2-year survival;Timepoint(s) of evaluation of this end point: 2 years after last patient has been enrolled in the trial

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Best response rate<br>- Progression free survival<br>- Overall survival<br>- Toxicity<br><br>Exploratory analyses:<br>- Prognostic and predictive role of clinical characteristics, tissue, blood and urine biomarkers in relation to the primary and secondary endpoints;Timepoint(s) of evaluation of this end point: The best response rates, progression free survival, toxicity, and health related quality of life will be reported within two years after enrollment of the last patient. The final survival analyses will be completed 5 years after enrollment of the last patient. By that time, we expect that also the exploratory analyses will be completed.