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Double Blind Placebo Controlled Controlled Study of Adjuvant MEDI4736 In Completely Resected NSCLC

This study is currently recruiting participants.
Verified March 2017 by Canadian Cancer Trials Group
Sponsor:
ClinicalTrials.gov Identifier:
NCT02273375
First Posted: October 24, 2014
Last Update Posted: October 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Intergroupe Francophone de Cancerologie Thoracique (IFCT)
Australasian Lung Cancer Trials Group
National Health and Medical Research Council, Australia
National Cancer Institute (NCI), Naples
Central and Eastern European Oncology Group
Dutch Society of Physicians for Pulmonology and Tuberculosis
Korean Cancer Study Group
Spanish Lung Cancer Group
West Japan Oncology Group (WJOG)
Chinese Thoracic Oncology Group
Information provided by (Responsible Party):
Canadian Cancer Trials Group
  Purpose
The purpose of this study is to find out whether it is better to receive a new drug, MEDI4736, or better to receive no further treatment after surgery (and possibly chemotherapy) for lung cancer.

Condition Intervention Phase
Non-Small Cell Lung Cancer Drug: MEDI4736 Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Prospective Double Blind Placebo Controlled Randomized Study of Adjuvant MEDI4736 In Completely Resected Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Canadian Cancer Trials Group:

Primary Outcome Measures:
  • Compare Disease free survival (DFS) for patients with NSCLC that is PD-L1 positive [ Time Frame: 5.5 years ]

Secondary Outcome Measures:
  • Compare Disease Free Survival in all randomized patients [ Time Frame: 7 years ]
  • Compare overall survival (OS) for patients with NSCLC that is PD-L1 positive [ Time Frame: 5.5 years ]
  • Compare overall survival for all randomized patients [ Time Frame: 7 years ]
  • Compare Lung cancer specific survival for patients with NSCLC that is PD-L1 positive and all randomized patients [ Time Frame: 7 years ]
  • Evaluate the nature, severity and frequency of adverse effects and tolerability of MEDI4736 [ Time Frame: every 6 months ]
    All patients who receive at least one dose of MEDI4376/placebo will be included in the safety analysis. Descriptive summary tables will be presented on safety parameters by treatment arm. There will be safety monitoring by the NCIC CTG Data Safety Monitoring Committee (DSMC) every 6 months

  • Evaluate the Quality of life between the two treatment arms in PD-L1+ patients and in all randomized patients. [ Time Frame: 5.5 years ]
    The quality of life (QoL) of patients will be assessed using EORTC QLQ-C30 and the lung cancer module (QLQ-LC13) incorporated.

  • Determine survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile [ Time Frame: 5.5 years ]
  • Determine the incremental cost effectiveness and cost utility ratios for MEDI4736 [ Time Frame: 5.5 years ]
  • Evaluate the predictive/prognostic significance of PD-L1 expression [ Time Frame: 5.5 years ]
  • Evaluation of changes in plasma/serum cytokines and other blood and tissue based biomarkers after treatment with MEDI4736 and at disease event [ Time Frame: 5.5 years ]
  • Explore polymorphisms that may be associated with outcomes [ Time Frame: Baseline only ]

Estimated Enrollment: 1100
Study Start Date: October 9, 2014
Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI4736
MEDI4736 by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier.
Drug: MEDI4736
Placebo Comparator: Placebo
PLACEBO by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier
Drug: Placebo

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung. according to WHO Classification of Tumours (WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. WHO/IARC Classification of Tumours, 4th Edition, Volume 7). Patients with large-cell neuroendocrine carcinomas are not eligible.
  • Patients must be classified post-operatively as Stage IB (≥ 4cm in the longest diameter), II or IIIA on the basis of pathologic criteria. Note: Although T3N2M0 tumours have been reclassified to stage IIIB in the 8th edition of the IASLC staging system, these patients remain eligible (as stage IIIA under the 7th edition criteria).

    • Complete surgical resection of the primary NSCLC is also mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour. Resection may be accomplished by open or VATS techniques

Note: Patients with synchronous primary tumours will not be eligible due to the potential uncertainty regarding their appropriate PD-L1 status.

Prior Systemic Therapy:

  • Pre-operative (neo-adjuvant) platinum based or other chemotherapy is not permissible.
  • Patients may have received prior post-operative platinum based chemotherapy as per standard of care.
  • No prior anticancer therapy for treatment of NSCLC other than standard post-operative adjuvant chemotherapy is permissible.

Radiation:

• Pre-operative or post-operative or planned radiation therapy is not permissible.

  • The patient must have an ECOG performance status of 0, 1.
  • Hematology: . Absolute neutrophil count ≥ 1.5 x 109/L or ≥ 1,500/µl Platelets ≥ 100 x 109/L or ≥ 100,000/µl
  • Biochemistry:

Total bilirubin* ≤ institutional upper limit of normal Alkaline phosphatase ≤ 2.5 x institutional upper limit of normal AST(SGOT) and ALT(SGPT) ≤ 2.5 x institutional upper limit of normal Creatinine Clearance ≥ 40 ml/min

* excluding Gilbert's syndrome

Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft Formula:

Females: GFR = 1.04 x (140-age) x weight in kg serum creatinine in μmol/L Males: GFR = 1.23 x (140-age) x weight in kg serum creatinine in μmol/L

  • Patient able and willing to complete the QoL, economics and other questionnaires. The baseline assessment must already have been completed within required timelines prior to randomization. Inability (illiteracy, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
  • Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
  • Protocol treatment is to begin within 2 working days of patient randomization

Exclusion Criteria:

  • Patients with a history of other malignancies, except:

    • adequately treated non-melanoma skin cancer,
    • curatively treated in-situ cancer, or
    • other malignancies curatively treated with no evidence of disease for ≥ 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
  • A combination of small cell and non-small cell lung cancer, pulmonary carcinoid tumour or large-cell neuroendocrine carcinoma (LCNEC).
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: patients with Grave's disease and/or psoriasis not requiring systemic therapy within the last two years from randomization and patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement are not excluded.
  • History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
  • Live attenuated vaccination administered within 30 days prior to randomization.
  • History of hypersensitivity to MEDI4736 or any excipient.
  • Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, must have a LVEF > 50% within 12 weeks prior to randomization.
  • Concurrent treatment with other investigational drugs or anti-cancer therapy.
  • Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to:

    • known clinical diagnosis of tuberculosis;
    • known active hepatitis B infection (positive HBV surface antigen (HBsAg)). Patients with a past or resolved hepatitis B infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBSAg) are eligible;
    • known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RA;
    • known human immunodeficiency virus infection (positive HIV antibodies).
    • known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function
  • Pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 14 days prior to randomization. Men and women of child-bearing potential must agree to use adequate contraception.
  Contacts and Locations
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): NCT02273375


Contacts
Contact: Chris O'Callaghan 613-533-6430 cocallaghan@ctg.queensu.ca

  Show 218 Study Locations
Sponsors and Collaborators
Canadian Cancer Trials Group
Intergroupe Francophone de Cancerologie Thoracique (IFCT)
Australasian Lung Cancer Trials Group
National Health and Medical Research Council, Australia
National Cancer Institute (NCI), Naples
Central and Eastern European Oncology Group
Dutch Society of Physicians for Pulmonology and Tuberculosis
Korean Cancer Study Group
Spanish Lung Cancer Group
West Japan Oncology Group (WJOG)
Chinese Thoracic Oncology Group
Investigators
Study Chair: Glenwood Goss Ottawa Hospital Research Institute, Ontario, Canada
  More Information

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT02273375     History of Changes
Other Study ID Numbers: BR31
IFCT1401 ( Other Identifier: Intergroupe Francophone de Cancerologie Thoracique (IFCT) )
ACTRN12615000323527 ( Registry Identifier: Australian New Zealand Clinical Trials Registry )
First Submitted: October 22, 2014
First Posted: October 24, 2014
Last Update Posted: October 11, 2017
Last Verified: March 2017

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
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs