Clinical Trials /

Survival imProvement in Lung cancEr iNduced by DenOsUmab theRapy

NCT02129699

Description:

The purpose of this study is to investigate how well the standard treatment (platinum-based doublet chemotherapy) in combination with denosumab works compared with the standard treatment alone in patients with a type of lung cancer called "non small cell lung cancer" (NSCLC) that has spread to other parts of the body.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Survival imProvement in <span class="go-doc-concept go-doc-disease">Lung cancEr</span> iNduced by <span class="go-doc-concept go-doc-intervention">DenOsUmab</span> theRapy

Title

  • Brief Title: Survival imProvement in Lung cancEr iNduced by DenOsUmab theRapy
  • Official Title: A Randomised, Open-label Phase III Trial Evaluating the Addition of Denosumab to Standard First-line Anticancer Treatment in Advanced NSCLC
  • Clinical Trial IDs

    NCT ID: NCT02129699

    ORG ID: ETOP 5-12 / EORTC 08111

    NCI ID: 2013-003156-21

    Trial Conditions

    Lung Cancer Non-small Cell Stage IV

    Trial Interventions

    Drug Synonyms Arms
    Denosumab XGEVA Standard chemotherapy + Denosumab

    Trial Purpose

    The purpose of this study is to investigate how well the standard treatment (chemotherapy)
    in combination with denosumab works compared with the standard treatment alone in patients
    with a type of lung cancer called "non small cell lung cancer" (NSCLC) that has spread to
    other parts of the body.

    Detailed Description

    The investigational medicinal product denosumab is a protein (monoclonal antibody) that
    works to slow down bone destruction caused by cancer spreading to the bone (bone
    metastasis). Denosumab is used in adults with cancer to prevent serious complications caused
    by bone metastasis (e.g. fracture, pressure on the spinal cord or the need to receive
    radiation therapy or surgery). Results from one study in lung cancer patients with bone
    metastasis suggested that adding denosumab to the standard chemotherapy may lead to a
    possible survival benefit.

    All patients will receive standard chemotherapy consisting of a combination of
    platinum-based agents plus gemcitabine or pemetrexed, depending on the nature of the lung
    cancer, every 3 weeks for about 3-4 months:

    Patients will be assigned to one of two groups, known as 'arms'.

    The treatment for each arm will be as follows:

    Arm A: 4 - 6 cycles of chemotherapy and best supportive care

    Arm B: 4 - 6 cycles of chemotherapy + denosumab 120 mg, administered subcutaneously every
    3-4 weeks.

    Denosumab treatment may continue thereafter until 2 years after the study has been
    evaluated.

    A total of 1000 patients from centers in Europe, Switzerland and Israel are expected to be
    enrolled in this study over a period of 37 months.The study will take approximately 51
    months to be completed

    Trial Arms

    Name Type Description Interventions
    None, standard chemotherapy only Other 4 - 6 cycles of standard chemotherapy + best supportive care. Standard chemotherapy consis of a combination of platinum-based agents plus gemcitabine or pemetrexed.
    Standard chemotherapy + Denosumab Experimental 4 - 6 cycles of standard chemotherapy + denosumab 120 mg, administered subcutaneously every 3-4 weeks. Standard chemotherapy consis of a combination of platinum-based agents plus gemcitabine or pemetrexed. Denosumab

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed advanced stage IV non-small cell lung
    carcinoma (NSCLC), according to 7th TNM classification

    - Age 18 years

    - ECOG performance status 0-2

    - Measurable or evaluable disease (according to RECIST 1.1 criteria)

    - Availability of tumour tissue for translational research:

    - preferred: FFPE block from primary tumour or metastasis,

    - alternatively: cell block

    - if no block available: 10 unstained slides with wax protection

    - Adequate haematological function: neutrophils 1.5 109/L, platelets

    100109/L, and hemoglobin 9 g/dL

    - Adequate liver function:

    - ALT 3 ULN ( 5 ULN if liver metastasis are present)

    - Total bilirubin < 2 x ULN

    - Adequate renal function: calculated creatinine clearance 30 mL/min (according to
    the formula of Cockroft-Gault)

    - Life expectancy of at least 3 months

    - 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 14
    days before beginning treatment

    - All sexually active men and women of childbearing potential must use an effective
    contraceptive method during the study treatment and for a period of at least 5 months
    following the last administration of trial treatment

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

    1. Trial treatment

    2. Submission of biomaterial for central testing

    Exclusion Criteria:

    - Patients with presence of documented sensitizing EGFR activating mutation or ALK
    rearrangements (screening following local standards is optional, but strongly
    encouraged in non-squamous histology)

    - Patients with documented brain metastases (systematic screening of patients not
    mandatory)

    - Prior chemotherapy or molecular targeted therapy for metastatic disease, with the
    exception of neoadjuvant or adjuvant chemotherapy or definitive radiochemotherapy, if
    terminated more than 6 months before registration.

    - Any investigational agent(s) within 30 days prior to randomisation

    - Concurrent bisphosphonate administration

    - Oral/ dental conditions (by visual inspection):

    - Prior history or current evidence of osteomyelitis / osteonecrosis of the jaw

    - Active dental or jaw condition which requires oral surgery

    - Planned invasive dental procedure for the course of the trial

    - Non-healed dental or oral surgery

    - Evidence of any medical condition which would impair the ability of the patient to
    participate in the trial or might preclude therapy with trial drugs (e.g. unstable or
    uncompensated respiratory, cardiac, hepatic or renal disease, active infection,
    uncontrolled diabetes mellitus; uncontrolled arterial hypertension 150/100 mmHg,
    history of myocardial infarction in the last 3 months)

    - Documented active infection with Hepatitis B virus or Hepatitis C virus, known
    infection with human immunodeficiency virus (HIV)

    - Known hypersensitivity to any of the components of the treatment

    - Severe, uncorrected hypocalcaemia or hypercalcaemia:

    - hypercalcaemia: total calcium >3.1 mmol/l, corrected calcium (with albumin level) >3
    mmol/l

    - hypocalcaemia: total calcium <2 mmol/l, corrected calcium (with albumin level) < 1.9
    mmol/l

    - Legal incapacity or limited legal capacity

    - Medical or psychological condition which in the opinion of the investigator would not
    permit the patient to complete the trial or sign meaningful informed consent

    - Women who are pregnant or breastfeeding

    - Any concurrent malignancy other than adequately treated basal or squamous cell
    carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast
    carcinoma. (Patients with a previous malignancy but without evidence of disease for
    2 years will be allowed to enter the trial)

    - Any previous exposure to denosumab, with the exception of a maximum of 2 previous
    doses of denosumab (Prolia) more than 6 month before enrolment for osteoporosis
    treatment/prevention

    - Previous bisphosphonate exposure which:

    - exceeds 2 prior doses of i.v. bisphosphonates AND/OR

    - exceeds a cumulative exposure of 1 year oral bisphosphonates

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall survival

    Secondary Outcome Measures

    Progression-free survival (PFS) based on RECIST 1.1

    Response based on RECIST 1.1

    Toxicity profile of denosumab

    Evaluation of potential predictive biomarkers for denosumab activity

    Trial Keywords

    NSCLC

    stage IV