A randomized phase II study comparing atezolizumab after concurrent chemo-radiotherapy with chemo-radiotherapy alone in limited disease small-cell lung cancer (ACHILES study)

Lung cancer is the most common cause of cancer-related deaths. Small-cell lung
cancer (SCLC) accounts for approx. 15% of the cases. Untreated, it is a very
aggressive disease with a poor prognosis (2-4 months). SCLC metastasizes
quickly and more frequently than other types of lung cancer. Up to 90 % of
patients respond to therapy, but most experience relapse. Only a few patients
are operable at the time of diagnosis. For inoperable disease, chemotherapy
(cisplatin plus etoposide) with concurrent radiotherapy is the main treatment
for patients with limited disease. Prophylactic cranial irradiation is
recommended. The 5-year survival is 25-30%. Thus there is a clear medical need
for new and better treatment options. Immunotherapy has been established as
both first- and second-line therapy in advanced non-small-cell lung cancer
(NSCLC). Immunotherapy is not yet established in the treatment of SCLC, but
several studies show promising results, that have led to new research
initiatives. In this study we would like to study the effects of the addition
of treatment with atezolizumab after standard treatment with chemo-radiotherapy
in limited disease SCLC.

This study has been transitioned to CTIS with ID 2024-515755-37-00 check the CTIS register for the current data.

Primary:
• To investigate whether adjuvant atezolizumab treatment after standard,
concurrent chemo-radiotherapy improves overall survival (OS) compared with no
treatment after standard, concurrent chemo-radiotherapy in limited disease SCLC
patients.
Secondary:
• Best response rates (BRR).
• Progression free survival (PFS).
• Toxicity.
• Health related quality of life.

Phase II, randomized, open-label study.
All participants will be treated with 4 courses of chemotherapy (platinum and
etoposide) and 30-40 fractions of radiotherapy (see protocol chapter 4).
Prophylactic cranial irradiation is recommended.
Patients who have completed the chemo-radiotherapy without major delays, who do
not show disease progression at the treatment evaluation visit (CT-scan) and
who have an adequate performance status will be randomized (1:1) to adjuvant
atezolizumab treatment every 3 weeks for 1 year or observation with no
treatment (as is the current standard of care).
Study duration 5 years.
Visit frequency during atezolizumab: every 3 weeks for 1 year.
Visit frequency follow-up: year 1-2-3: every 3 months; year 4-5: every 6 months.
160 randomized patients (212 to be included).

Treatment with chemo-radiotherapy with or without adjuvant follow-up treatment
with atezolizumab.

Risk: Adverse effects of study treatment.
Burden:
Screening (2-4 weeks), 4 courses of chemotherapy, 30-40 fractions of
radiotherapy, 50% of patients: atezolizumab adjuvant therapy for 1 year.
Treatment:
Etoposide: I.V. infusion 500 mL every 3 weeks (30 min per infusion, day 1-3, 4
cycles)
Cisplatin or carboplatin: I.V. infusion 1.000 mL every 3 weeks (2 h per
infusion, day 1, 4 cycles)
Atezolizumab: I.V. infusion 500 mL every 3 weeks (30-60 min per infusion, day
1, 1 year)
Study procedures:
Physical examination: (almost) every cycle; follow-up: 2-4 times/year.
Blood tests: every cycle; follow-up: 2-4 times/year, 10-25 mL per occasion.
MRI brain: during screening (in line with standard treatment).
PET CT-scan: during screening (in line with standard treatment).
CT-scan thorax and abdomen: every 3-6 months (in line with standard treatment).
Tumor biopsy: 0-1.
Pregnancy test (if relevant): every months for 17 months.
Pulmonary function test: 1.
Questionnaires EORTC QLQ-C30 and LC13 : every 3 months for 2,5 years.
Optional: Tumor biopsy at disease progression.