Clinical Trials /

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

NCT02273375

Description:

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.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Double Blind Placebo Controlled Controlled Study of Adjuvant MEDI4736 In Completely Resected NSCLC
  • Official Title: A Phase III Prospective Double Blind Placebo Controlled Randomized Study of Adjuvant MEDI4736 In Completely Resected Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: BR31
  • SECONDARY ID: IFCT1401
  • SECONDARY ID: ACTRN12615000323527
  • NCT ID: NCT02273375

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
MEDI4736MEDI4736
PlaceboPlacebo

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.

Trial Arms

NameTypeDescriptionInterventions
MEDI4736ExperimentalMEDI4736 by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier.
  • MEDI4736
PlaceboPlacebo ComparatorPLACEBO by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier
  • Placebo

Eligibility 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:

        • 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Compare Disease free survival (DFS) for patients with NSCLC that is PD-L1 positive
Time Frame:6.7 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Compare overall survival (OS) for patients with NSCLC that is PD-L1 positive
Time Frame:8 years
Safety Issue:
Description:
Measure:Compare overall survival for all randomized patients
Time Frame:8 years
Safety Issue:
Description:
Measure:Compare Lung cancer specific survival for patients with NSCLC that is PD-L1 positive and all randomized patients
Time Frame:8 years
Safety Issue:
Description:
Measure:Evaluate the nature, severity and frequency of adverse effects and tolerability of MEDI4736
Time Frame:every 6 months
Safety Issue:
Description: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
Measure:Evaluate the Quality of life between the two treatment arms in PD-L1+ patients and in all randomized patients.
Time Frame:8 years
Safety Issue:
Description:The quality of life (QoL) of patients will be assessed using EORTC QLQ-C30 and the lung cancer module (QLQ-LC13) incorporated.
Measure:Determine survival benefits participants judge necessary to make adjuvant immunotherapy worthwhile
Time Frame:8 years
Safety Issue:
Description:
Measure:Determine the incremental cost effectiveness and cost utility ratios for MEDI4736
Time Frame:8 years
Safety Issue:
Description:
Measure:Evaluate the predictive/prognostic significance of PD-L1 expression
Time Frame:8 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Explore polymorphisms that may be associated with outcomes
Time Frame:Baseline only
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Canadian Cancer Trials Group

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