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No longer recruiting (closed or complete)Last updated: 13 January 2025

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

Trial purpose

Medical clipboardCancer treatment

Tumor type

Lung Cancers Lung cancer

Age

People18+

Trial acronym

STIMULI

Clinical summary

Summary

In this trial, participants will be randomised to the experimental treatment or observation arm. In the experimental arm, participants will receive Nivolumab (1mg/kg IV) and Ipilimumab (3mg/kg IV) as induction therapy once every three weeks for four cycles, followed by 240mg Nivolumab IV as maintenance therapy once every two weeks for a maximum of 12 months.

Conditions

This trial is treating people with limited small cell lung cancer (SCLC)

Eligibility

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.

Exclusion

Exclusion Criteria for enrolment:

  • Patient with mixed small-cell and non-small-cell histologic features
  • Patient with pleural or pericardial effusions proven to be malignant
  • Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast (if no RT was involved).
  • Patients with other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient's capacity to participate in the study.
  • Ongoing clinically serious infections requiring systemic antibiotic or antiviral, antimicrobial, antifungal therapy.
  • Known or suspected hypersensitivity to nivolumab or ipilimumab or any of their excipients.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  • Documented history of severe autoimmune or immune mediated symptomatic disease that required prolonged (more than 2 months) systemic immunosuppressive (e.g. steroids) treatment, such as but not limited to ulcerative colitis and Crohn´s disease, rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, or autoimmune vasculitis (eg, Wegener's granulomatosis).
  • Subjects with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment.
  • Interstitial lung disease or pulmonary fibrosis
  • Women who are pregnant or in the period of lactation.
  • Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
  • Patients with any concurrent anticancer systemic therapy (except for chemotherapy cycle 1).
  • HIV, active Hepatitis B or Hepatitis C infection
  • Previous radiotherapy to the thorax (prior to inclusion), including RT for breast cancer
  • Planned radiotherapy to lung of mean dose > 20 Gy or V20 > 35 %
  • Patients who received treatment with an investigational drug agent during the 3 weeks before enrolment in the study.
  • Prior chemotherapy or radiotherapy for SCLC. Exception: one cycle of chemotherapy (as specified to section 10.2) may be administered prior to enrolment.

Exclusion criteria for randomisation:

  • Less than 4 cycles of chemotherapy administered, less than 85% PTV of thoracic radiotherapy delivered, or PCI not completed
  • Progressive disease after chemo-radiotherapy and PCI

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You are currently being treated on a clinical trial.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Bristol-Myers Squibb (BMS),Ludwig Institute for Cancer Research,European Thoracic Oncology Platform

Scientific Title

A Randomised Open-label Phase II Trial of Consolidation With Nivolumab and Ipilimumab in Limited-stage SCLC After Chemo-radiotherapy

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