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Avelumab in Non-Small Cell Lung Cancer (JAVELIN Lung 200)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
ClinicalTrials.gov Identifier:
NCT02395172
First received: February 27, 2015
Last updated: February 16, 2017
Last verified: February 2017
  Purpose
To demonstrate superiority with regard to overall survival of avelumab versus docetaxel in subjects with programmed death ligand 1 (PD-L1) positive, non-small cell lung cancer (NSCLC) after failure of a platinum-based doublet.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung Drug: Avelumab Drug: Docetaxel Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase III Open-label, Multicenter Trial of Avelumab (MSB0010718C) Versus Docetaxel in Subjects With Non-small Cell Lung Cancer That Has Progressed After a Platinum-containing Doublet

Resource links provided by NLM:


Further study details as provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Primary Outcome Measures:
  • Overall survival (OS) time [ Time Frame: Time from date of randomization until death, assessed up to 7.6 years ]
    The OS is defined as the time from randomization to death due to any cause.


Secondary Outcome Measures:
  • Progression-Free Survival (PFS) Time [ Time Frame: Time from date of randomization until progressive disease or death, assessed up to 6.5 years ]
    PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PFS will be assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD is defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Best Overall Response (BOR) [ Time Frame: Time from date of randomization up to 6.5 years ]
    BOR will be determined according to RECIST 1.1 and as adjudicated by an IERC. BOR is defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  • Change from baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire [ Time Frame: Baseline up to 6.5 years ]
    The EQ-5D-5L Health Outcome Questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items are combined to generate health profiles. These profiles were converted to a continuous single index score using a one to one matching. The lowest possible score is -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest is 1.00 (no problems in all 5 dimensions).

  • Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status [ Time Frame: Baseline up to 6.5 years ]
    EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer subjects. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.

  • Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline up to 6.5 years ]
    EORTC QLQ-LC13 consists of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprises 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, neuropathy, alopecia, and medicine for pain). Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).

  • Number of subjects with Treatment-Emergent Adverse Events (TEAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 [ Time Frame: From the first dose of study drug treatment up to 30 days after the last dose of study drug administration, assessed up to 6.5 years ]
    TEAEs will be defined as the adverse events (AEs) that occur between first dose of study drug administration and 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.


Enrollment: 792
Study Start Date: March 2015
Estimated Study Completion Date: January 2023
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avelumab Drug: Avelumab
Subjects will receive 10 milligram per kilogram (mg/kg) of avelumab as a 1-hour intravenous (IV) infusion once every 2 weeks.
Active Comparator: Docetaxel Drug: Docetaxel
Subjects will receive 75 mg per square meter (m^2) (per label) of docetaxel by IV infusion once every 3 weeks.

  Eligibility

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

Inclusion Criteria

  • Signed written informed consent before any trial related procedure
  • Male or female subjects aged greater than or equal to (>=) 18 years
  • Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment
  • Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory
  • Subjects with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression
  • Subjects must have progressed after an acceptable therapy defined as follows:

    1. Subjects must have progressed during or after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease. A history of continuation (use of a non platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination OR
    2. Subjects must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease
  • Subjects with non-squamous cell NSCLC of unknown epidermal growth factor receptor (EGFR) mutation status will require testing (local laboratory, or central laboratory if local testing is not available). Subjects with a tumor that harbors an activating EGFR mutation will not be eligible
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
  • Estimated life expectancy of more than 12 weeks
  • Adequate hematological function defined by White Blood Cell (WBC) count >= 2.5 × 10^9/L with absolute neutrophil count (ANC) >= 1.5 × 10^9/L, lymphocyte count >=0.5 × 10^9/L, platelet count >= 100 × 10^9/L, and hemoglobin >= 9 gram per deciliter (g/dL) (may have been transfused)
  • Adequate hepatic function defined by a total bilirubin level less than or equal to (<=) 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels <= 2.5 × ULN for all subjects
  • Adequate renal function defined by an estimated creatinine clearance > 30 milliliter per minute (mL/min) according to the Cockcroft-Gault formula (or local institutional standard method).

Other protocol defined inclusion criteria could apply

Exclusion criteria

  • In the United States only, subjects with a squamous cell histology will be excluded
  • Systemic anticancer therapy administered after disease progression during or following a platinum based combination
  • Subjects with non-squamous cell NSCLC whose disease harbors EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Subjects of unknown ALK and/or EGFR mutation status will require testing at screening (local laboratory, or central laboratory if local testing is not available)
  • Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as PD-1, PD L1, or cytotoxic T lymphocyte antigen-4 (CTLA-4).
  • Concurrent anticancer treatment
  • Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the subject has not fully recovered from the surgery within 4 weeks of randomization
  • Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment.
  • All subjects with brain metastases, except those meeting the following criteria:

    1. Brain metastases have been treated locally, and
    2. No ongoing neurological symptoms that are related to the brain localization of the disease
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:

    1. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
    2. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to (<=)10 milligram (mg) or equivalent prednisone per day
    3. Administration of steroids through a route known to result in a minimal systemic exposure are acceptable
  • Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be <=10 mg per day of equivalent prednisone

Other protocol defined exclusion criteria could apply

  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: NCT02395172

  Show 260 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02395172     History of Changes
Other Study ID Numbers: 100070-004
2014-005060-15 ( EudraCT Number )
Study First Received: February 27, 2015
Last Updated: February 16, 2017

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
avelumab
MSB0010718C
Non-Small Cell Lung Cancer
Anti-PD-L1

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 23, 2017