STIMULI: This phase II trial is evaluating the efficacy (how well the treatment works) and tolerability (how severe the side effects are) of the standard treatment (chemotherapy and radiotherapy) alone and in combination with immunotherapy drugs (nivolumab and ipilimumab) in patients with limited small cell lung cancer (SCLC)A Randomised Open-label Phase II Trial of Consolidation With Nivolumab and Ipilimumab in Limited-stage SCLC After Chemo-radiotherapy

Inclusion

Inclusion Criteria for enrolment:

• Histologically or cytologically confirmed small cell lung carcinoma
• Untreated limited stage disease ((with the exception of one cycle of chemotherapy given prior to enrolment) as defined by stage I-IIIB based on 7th TNM classification (IASLC classification for SCLC proposal). M0 proven by
• Whole body FDG-PET CT including a contrast-enhanced CT of thorax and upper abdomen (incl. liver, kidney, adrenals); OR contrast-enhanced CT of thorax and upper abdomen (incl. liver, kidney, adrenals) and bone scan; AND
• brain MRI (or contrast enhanced CT of the brain). . within 28 days before start of chemotherapy.
• Age ≥ 18 years
• ECOG performance status 0-1
• Adequate haematological function:
• haemoglobin > 9 g/dL
• neutrophils count >1.5×109/L
• platelet count > 100 × 109/L
• Adequate liver function:
• Total bilirubin < 2.5 × ULN
• ALT and/or AST < 2.5 × ULN
• alkaline phosphatase < 5 ULN.
• Adequate renal function: Calculated creatinine clearance ≥ 30 mL/min (Cockroft-Gault)
• Pulmonary function FEV1 of 1.0L or > 40% predicted value and DLCO > 40% predicted value.
• Patient capable of proper therapeutic compliance, and accessible for correct follow-up.
• Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before beginning of chemotherapy.
• All sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs.
• Measurable or evaluable disease (according to RECIST 1.1 criteria). Not eligible: patients with only one measurable or evaluable tumour lesion which was resected or irradiated prior to enrolment.

• Written Informed Consent (IC) must be signed and dated by the patient and the investigator prior to any trial-related intervention for

  1. Chemo-radiotherapy treatment and PCI, and subsequent randomisation, including mandatory biological samples
  2. Optional biological material collection, long-term storage and future use of biological material for translational research

Inclusion Criteria for randomisation:

• Chemo-radiotherapy completed per protocol: 4 cycles of chemotherapy, ≥85% of PTV of thoracic radiotherapy, as well as completed, mandatory PCI
• non-PD after chemo-radiotherapy and PCI
• ECOG performance status 0-2
• Recovery of all adverse events to a grade ≤1, except for fatigue, appetite, oesophagitis and renal impairment (where ≤2 is allowed) and alopecia (any grade)
• Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before randomisation.