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Small Cell Lung Carcinoma Trial With Nivolumab and IpiliMUmab in LImited Disease (STIMULI)

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ClinicalTrials.gov Identifier: NCT02046733
Recruitment Status : Recruiting
First Posted : January 28, 2014
Last Update Posted : February 20, 2018
Sponsor:
Collaborators:
Intergroupe Francophone de Cancerologie Thoracique
Ludwig Center for Cancer Research of Lausanne
Frontier Science Foundation, Hellas
Bristol-Myers Squibb
Information provided by (Responsible Party):
European Thoracic Oncology Platform

Brief Summary:

Despite the fact that the majority of the patients with limited disease SCLC will respond very well to the standard treatment, a great proportion will relapse within 12 - 24 months.

Several studies in patients with lung cancer suggested a possible favourable association between the increased presence of immunologically active cells in the tumour and survival. Nivolumab and ipilimumab are proteins, which help your immune system to attack and destroy cancer cells by your immune cells. Early clinical trials with nivolumab and ipilimumab have shown activity in a broad range of cancers, including SCLC.

The aim of the current study is to investigate the efficacy (how well the treatment works) and tolerability (how severe the side effects are) of the standard treatment (chemotherapy and radiotherapy) alone, compared with the standard treatment followed by nivolumab and ipilimumab in patients with limited SCLC.


Condition or disease Intervention/treatment Phase
Limited Stage Small Cell Lung Cancer Small Cell Lung Cancer Drug: Ipilimumab Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Open-label Phase II Trial of Consolidation With Nivolumab and Ipilimumab in Limited-stage SCLC After Chemo-radiotherapy
Actual Study Start Date : July 28, 2014
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Nivolumab + Ipilimumab

- Induction: Nivolumab at a dose of 1 mg/kg i.v. followed (on the same day) by Ipilimumab at a dose of 3 mg/kg i.v. once every 3 weeks, 4 cycles

- Maintenance: Nivolumab 240 mg i.v. once every 2 weeks, for a maximum of 12 months from start of maintenance

Drug: Ipilimumab
Induction phase: i.v. 3 mg/kg, once every 3 weeks × 4 cycles, to start within 6-8 weeks (42-56 days) from start of chemotherapy cycle 4, and not more than 2 weeks (14 days) after the date of randomisation)
Other Name: Yervoy

Drug: Nivolumab
Induction phase: Nivolumab i.v. 1 mg/kg, once every 3 weeks × 4 cycles, to start within 6-8 weeks (42-56 days) from start of chemotherapy cycle 4, and not more than 2 weeks (14 days) after the date of randomisation) Maintenance Phase: Nivolumab 240 mg i.v once every 2 weeks for a maximum of 12 months from start of maintenance (the first dose of maintenance nivolumab will be administered 3 weeks after the last IMP doses of induction Phase).
Other Name: Opdivo

No Intervention: Observation
no further treatment; tumour assessment, follow-up documentation and collection of biological material will be done according to the same schedule as Arm 1.



Primary Outcome Measures :
  1. Overall survival [ Time Frame: From date of randomisation until death from any cause, assessed up to a maximum of 6,5 years ]
    Defined as time from the date of randomisation until death from any cause. Censoring will occur at the last follow-up date.

  2. Progression-free survival determined by RECIST 1.1 [ Time Frame: From date of randomisation until documented progression or death, if progression is not documented, assessed up to a maximum of 6,5 years ]
    Defined as time from the date of randomisation until documented progression or death, if progression is not documented. Censoring will occur at the last tumor assessment only if patient is lost to follow-up.


Secondary Outcome Measures :
  1. Objective response [ Time Frame: From randomisation to termination of trial treatment, up to a maximum of 2 years ]

    Objective response is defined as best overall response (CR or PR) across all assessment time-points during the period from randomisation to termination of trial treatment.

    Objective response to chemo-radiotherapy will be determined by tumour assessment around week 15.

    Objective response to trial treatment will be determined using RECIST 1.1 criteria


  2. Time to treatment failure [ Time Frame: From date of randomisation until discontinuation of treatment for any reason, assessed up to a maximum of 6.5 years ]
    Defined as time from the date of randomisation to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death). Censoring will occur at the last follow-up date.

  3. Toxicity [ Time Frame: Up to a maximum of 6.5 years ]
    Adverse events classified according to NCI CTCAE version 4.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02046733


Contacts
Contact: Barbara Ruepp +41 31 389 93 91 STIMULI@etop-eu.org

  Show 51 Study Locations
Sponsors and Collaborators
European Thoracic Oncology Platform
Intergroupe Francophone de Cancerologie Thoracique
Ludwig Center for Cancer Research of Lausanne
Frontier Science Foundation, Hellas
Bristol-Myers Squibb
Investigators
Study Chair: Solange Peters, MD PhD European Thoracic Oncology Platform (ETOP)
Study Chair: Dirk De Ruysscher, MD PhD Maastro Clinic, Maastricht, The Netherlands

Additional Information:
Publications:
Responsible Party: European Thoracic Oncology Platform
ClinicalTrials.gov Identifier: NCT02046733     History of Changes
Other Study ID Numbers: ETOP/IFCT 4-12
2013-002609-78 ( EudraCT Number )
CA184-310 ( Other Identifier: Bristol-Myers Squibb )
SNCTP000000166 ( Registry Identifier: Swiss National Clinical Trials Portal (SNCTP) )
First Posted: January 28, 2014    Key Record Dates
Last Update Posted: February 20, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by European Thoracic Oncology Platform:
SCLC
CTLA-4

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs