COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    NCT02273375
Previous Study | Return to List | Next Study

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02273375
Recruitment Status : Active, not recruiting
First Posted : October 24, 2014
Last Update Posted : April 3, 2020
Sponsor:
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
Fundación GECP
West Japan Oncology Group (WJOG)
Chinese Thoracic Oncology Group
Information provided by (Responsible Party):
Canadian Cancer Trials Group

Tracking Information
First Submitted Date  ICMJE October 22, 2014
First Posted Date  ICMJE October 24, 2014
Last Update Posted Date April 3, 2020
Actual Study Start Date  ICMJE October 9, 2014
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2020)
  • Compare Disease free survival (DFS) for patients with NSCLC that is PD-L1 expression TC ≥ 25%, in patients with PD-L1 expression TC ≥ 1% [ Time Frame: 6.7 years ]
  • Compare Disease Free Survival in all randomized patients [ Time Frame: 6.7 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 22, 2014)
Compare Disease free survival (DFS) for patients with NSCLC that is PD-L1 positive [ Time Frame: 5.5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2020)
  • Compare overall survival (OS) for patients with PD-L1 [ Time Frame: 8 years ]
  • ≥ 25%, PD-L1 ≥ 1%, and in all randomized patients [ Time Frame: 8 years ]
  • Compare Lung cancer specific survival for patients with NSCLC that is PD-L1 positive and all randomized patients [ Time Frame: 8 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 ≥ 25%, PD-L1 ≥ 1% and in all randomized patients [ Time Frame: 8 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: 8 years ]
  • Determine the incremental cost effectiveness and cost utility ratios for MEDI4736 [ Time Frame: 8 years ]
  • Evaluate the predictive/prognostic significance of PD-L1 expression [ Time Frame: 8 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: 8 years ]
  • Explore polymorphisms that may be associated with outcomes [ Time Frame: Baseline only ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2014)
  • 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. [ 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) questionnaires
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Double Blind Placebo Controlled Controlled Study of Adjuvant MEDI4736 In Completely Resected NSCLC
Official Title  ICMJE A Phase III Prospective Double Blind Placebo Controlled Randomized Study of Adjuvant MEDI4736 In Completely Resected Non-Small Cell Lung Cancer
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: MEDI4736
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: MEDI4736
    MEDI4736 by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier.
    Intervention: 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
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 26, 2018)
1360
Original Estimated Enrollment  ICMJE
 (submitted: October 22, 2014)
1100
Estimated Study Completion Date  ICMJE January 31, 2024
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

• Patients with N2 disease only who receive adjuvant post-operative radiation therapy are eligible provided they meet the protocol specified timing criteria for surgery, adjuvant chemotherapy and randomization. Pre-operative 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Bulgaria,   Canada,   China,   France,   Hungary,   Italy,   Japan,   Korea, Republic of,   Netherlands,   New Zealand,   Poland,   Romania,   Singapore,   Spain,   Taiwan,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02273375
Other Study ID Numbers  ICMJE BR31
IFCT1401 ( Other Identifier: Intergroupe Francophone de Cancerologie Thoracique (IFCT) )
ACTRN12615000323527 ( Registry Identifier: Australian New Zealand Clinical Trials Registry )
U1111-1238-5923 ( Other Identifier: WHO )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Canadian Cancer Trials Group
Study Sponsor  ICMJE Canadian Cancer Trials Group
Collaborators  ICMJE
  • 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
  • Fundación GECP
  • West Japan Oncology Group (WJOG)
  • Chinese Thoracic Oncology Group
Investigators  ICMJE
Study Chair: Glenwood Goss Ottawa Hospital Research Institute, Ontario, Canada
PRS Account Canadian Cancer Trials Group
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP