E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Limited disease small-cell lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
Inoperable small-cell lung cancer if all lesions can be included in a tolerable radiotherapy field; i.e. confined to one hemithorax plus mediastinal, hilar and supraclavicular lymph nodes |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041069 |
E.1.2 | Term | Small cell lung cancer limited stage |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The exploratory analyses will be conducted as a substudy. Due to the rapid development of knowledge and technology within this field, we will outline a detailed project plan when the last patient has been enrolled. We expect to the complete this subproject within 5 years of enrollment of the last patient. |
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E.3 | Principal 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 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
2 years after last patient has been enrolled in the trial |
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E.5.2 | Secondary end point(s) |
- Best response rate
- Progression free survival
- Overall survival
- Toxicity
Exploratory analyses:
- Prognostic and predictive role of clinical characteristics, tissue, blood and urine biomarkers in relation to the primary and secondary endpoints |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 18 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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According to the trial design, the study treatment will continue for a maximum of 12 months after chemo-radiotherapy for patients randomized to the experimental arm. Data collection will be completed 5 years after enrollment of the last patient. Studies show that immunotherapy might provide long term survival in some patients. Thus, 5 year survival is an endpoint of great interest. The exploratory analyses will start after enrollment is completed and is expected to take several years.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 6 |