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Trial record 5 of 38 for:    small cell lung ca | Recruiting, Not yet recruiting, Available Studies

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

This study is currently recruiting participants.
See Contacts and Locations
Verified November 2016 by European Thoracic Oncology Platform
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
ClinicalTrials.gov Identifier:
NCT02046733
First received: January 17, 2014
Last updated: November 1, 2016
Last verified: November 2016
  Purpose

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 Intervention Phase
Limited Stage Small Cell Lung Cancer Small Cell Lung Cancer Drug: Ipilimumab Drug: Nivolumab Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by European Thoracic Oncology Platform:

Primary Outcome Measures:
  • 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.

  • 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:
  • 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


  • 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.

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


Estimated Enrollment: 260
Study Start Date: July 2014
Estimated Study Completion Date: January 2022
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02046733

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

  Hide Study Locations
Locations
Belgium
University Hospital Gasthuisberg, KU Leuven Not yet recruiting
Leuven, Belgium, 3000
Principal Investigator: Kristiaan Nackaerts         
France
Avignon - Institut Sainte-Catherine Not yet recruiting
Avignon, France
Principal Investigator: Hilgers Werner         
Caen - Centre François Baclesse Recruiting
Caen, France
Principal Investigator: Radj Gervais         
CHU Recruiting
Caen, France
Principal Investigator: Gérard Zalcman         
Percy/Armées Recruiting
Clamart, France
Principal Investigator: Hervé Le Floch         
Clermont-Ferrand Not yet recruiting
Clermont-Ferrand, France
Principal Investigator: Patrick Merle         
Créteil - CHI Recruiting
Creteil, France
Principal Investigator: Isabelle Monnet         
CHU Recruiting
Grenoble, France
Principal Investigator: Denis Moro-Sibilot         
Centre Hospitalier Général Recruiting
Le Mans, France, 72037
Principal Investigator: Olivier Molinier, Dr         
Hôpital Louis Pradel Recruiting
Lyon, France
Principal Investigator: Nicolas Girard         
Lyon - Sud Recruiting
Lyon, France
Principal Investigator: Pierre-Jean Souquet         
AP-HM Recruiting
Marseille, France
Principal Investigator: Fabrice Barlesi         
Centre Hospitalier Universitaire de Montpellier Recruiting
Montpellier, France
Principal Investigator: Jean-Louis Pujol, MD         
CH Recruiting
Mulhouse, France
Principal Investigator: Didier Debieuvre         
CRLCC Recruiting
Nantes, France
Principal Investigator: Jaafar Bennouna         
Nice - CRLCC Recruiting
Nice, France
Principal Investigator: Michel Poudenx         
Orléans - CH Not yet recruiting
Orléans, France
Principal Investigator: Adrien Dixmier         
Paris - Bichat Recruiting
Paris, France
Principal Investigator: Gérard Zalcman         
Paris - Saint-Louis Recruiting
Paris, France
Principal Investigator: Damien Pouessel         
Paris - Tenon Recruiting
Paris, France
Principal Investigator: Jacques Cadranel         
CHU Recruiting
Rennes, France
Principal Investigator: Hervé Lena         
Nouvel Hôpital Civil Recruiting
Strasbourg, France
Principal Investigator: Elisabeth Quoix         
Suresnes Recruiting
Suresnes, France
Principal Investigator: Sylvie Friard         
CHI Recruiting
Toulon, France
Principal Investigator: Clarisse Audigier-Valette         
CHU Recruiting
Toulouse, France
Principal Investigator: Julien Mazieres         
CHU Recruiting
Tours, France
Principal Investigator: Eric Pichon         
Institut Gustave Roussy Recruiting
Villejuif, France
Principal Investigator: Cécile Le Péchoux         
Germany
Klinikum Esslingen Recruiting
Esslingen, Germany
Principal Investigator: Martin Faehling         
LungenClinic Grosshansdorf GmbH Recruiting
Grosshansdorf, Germany, 22927
Principal Investigator: Martin Reck, PD Dr. med.         
Klinikum München-Bogenhausen Recruiting
München, Germany
Principal Investigator: Martin Schütz         
Thoracic Oncology Centre Munich Recruiting
München, Germany
Principal Investigator: Rudolf M Huber, Prof.         
Pius-Hospital Oldenburg Recruiting
Oldenburg, Germany
Principal Investigator: Frank Griesinger         
Krankenhaus der Barmherzigen Brüder Recruiting
Trier, Germany
Principal Investigator: Heinz Kirchen, Dr.         
Universitätsklinikum Tübingen Recruiting
Tübingen, Germany
Principal Investigator: Frank Heinzelmann         
Netherlands
VUMC Recruiting
Amsterdam, Netherlands
Principal Investigator: Joop de Langen         
Maastro Clinic Recruiting
Maastricht, Netherlands
Principal Investigator: Dirk De Ruysscher         
Spain
Hospital General Universitario Alicante Recruiting
Alicante, Spain
Principal Investigator: Bartomeu Massutí         
Hospital Universitario Cruces Recruiting
Barakaldo, Spain
Principal Investigator: Guillermo López Vivanco         
Hospital De La Santa Creu I Sant Pau Recruiting
Barcelona, Spain
Principal Investigator: Margarita Majem         
Clinico San Carlos Not yet recruiting
Madrid, Spain
Principal Investigator: Jose Luis González Larriba         
Hospital Puerta de Hierro Not yet recruiting
Madrid, Spain
Principal Investigator: Mariano Provencio Pulla         
Hospital Universitario 12 Octubre Recruiting
Madrid, Spain
Principal Investigator: Santiago Ponce Aix         
Hospital Universitario Fundacion Jimenez Díaz Recruiting
Madrid, Spain
Principal Investigator: Manuel Domine         
Hospital Universitario Central De Asturias Recruiting
Oviedo, Spain
Principal Investigator: Neomi Villanueva         
Hospital Virgen De La Salud Recruiting
Toledo, Spain
Principal Investigator: Antonio Irigoyen         
Hospital Clínico Universitario De Valencia Recruiting
Valencia, Spain
Principal Investigator: Amelia Insa Mollá         
Switzerland
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland
Principal Investigator: Solange Peters, MD PhD         
University Hospital Zürich Recruiting
Zürich, Switzerland
Principal Investigator: Alessandra Curioni         
United Kingdom
Clatterbridge Cancer Centre NHS Not yet recruiting
Liverpool, United Kingdom
Principal Investigator: Pieter Postmus         
Royal Marsden Not yet recruiting
London, United Kingdom
Principal Investigator: Sanjay Popat         
Christie Hospital Not yet recruiting
Manchester, United Kingdom
Principal Investigator: Raffaele Califano         
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
  More Information

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) )
Study First Received: January 17, 2014
Last Updated: November 1, 2016
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
Lung Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 25, 2017