Clinical Trials /

The Addition of Metformin to Definitive Radiotherapy in Patients With Stage III NSCLC

NCT04170959

Description:

Study the effect of metformin when added to definitive locoregional radiotherapy on locoregional control and relapse rate in stage III non-small cell lung cancer patients receiving sequential chemoradiotherapy. Try to identify subsets of patients who derive maximum benefit of adding metformin to radiotherapy using innovative biomarkers.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Addition of Metformin to Definitive Radiotherapy in Patients With Stage III NSCLC
  • Official Title: Randomized Phase II Trial of Definitive Radiotherapy With or Without metFORMin in Patients With Inoperable Stage III Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: OPM-RADFORMIN-1801
  • NCT ID: NCT04170959

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
MetforminC: Interventional arm

Purpose

Study the effect of metformin when added to definitive locoregional radiotherapy on locoregional control and relapse rate in stage III non-small cell lung cancer patients receiving sequential chemoradiotherapy. Try to identify subsets of patients who derive maximum benefit of adding metformin to radiotherapy using innovative biomarkers.

Detailed Description

      The administration of oral metformin during radiotherapy is thought to decrease the hypoxic
      fraction of tumour cells, improving radiosensitivity and promoting apoptosis, resulting in
      better outcome. This hypothesis will be evaluated in a trial with randomized design. All
      patients willing to participate will receive definitive radiotherapy, either in combination
      with metformin (arm C) or without metformin (arm B). Patients who refuse to participate in
      the randomized part can be included in the observational arm of the study (arm A). In
      addition, the validated biomarker of tumour hypoxia (18F-HX4 PET/CT scintigraphy
      (18F-flortanidazole positron emission computed tomography) and biomarkers of resistance,
      apoptosis and glucose metabolism will be evaluated for their potential predictive value.
    

Trial Arms

NameTypeDescriptionInterventions
A: Observational armNo InterventionRadiotherapy as per standard of care without metformin, no additional biomarkers/imaging will be performed
    B: Control armOtherRadiotherapy as per standard of care without metformin, with additional biomarkers/imaging
      C: Interventional armActive ComparatorRadiotherapy as per standard of care with metformin, with additional biomarkers/imaging
      • Metformin

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Provision of signed and dated informed consent form.
      
                -  Stated willingness to comply with all study procedures and availability for the
                   duration of the study.
      
                -  Ability to take oral medication and willing to adhere to the RADFORMIN-regimen.
      
                -  Male or female, ≥ 18 years of age.
      
                -  Histological or cytological proven stage III NSCLC after adequate staging with at
                   least 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT, contrast enhanced CT-thorax and
                   contrast-enhanced CT/MRI brain. (According to 8th edition of TNM classification (=
                   tumor, node, metastasis))
      
                -  Absence of diabetes, (diabetes is defined as fasting plasma glucose >126 mg/dL or
                   random plasma glucose >200 mg/dL).
      
                -  Eastern Cooperative Oncology Group (ECOG) performance score (= World Health
                   Organization (WHO) score) of 0-1.
      
                -  Adequate hematologic, hepatic and renal function as clinically acceptable in the
                   opinion of the Primary Investigator.
      
                -  Adequate pulmonary function in order to be administered definitive radiotherapy. With
                   Forced Expiratory Volume (FEV) > 1.2 litres per second or more than 50% of predicted,
                   and diffusion capacity of lung for carbon monoxide (DLCO) > 40% predicted. (Values
                   without administration of medical bronchodilation. In case of Tiffeneau < 70%
                   bronchodilation will be administered)
      
                -  Having received at least 2 cycles of platinum-based chemotherapy. This according to
                   institutional standards and without progression (on a restaging CT-scan within 3 weeks
                   after day 1 of the last given cycle, according to RECIST criteria).
      
              Exclusion Criteria:
      
                -  Current use of metformin, insulin or other oral antidiabetic drugs
                   (thiazolidinediones, sulfonylureas, mitiglinides, alpha-glucosidase inhibitors,
                   incretin mimetics, dipeptidyl peptidase-4 inhibitors, amylin analogues,
                   sodium-glucose-cotransporter-2 (SGLT-2)-inhibitors) for any reason.
      
                -  Evidence for metastatic disease.
      
                -  Conditions associated with increased risk of metformin-associated lactic acidosis: New
                   York Heart Association class III or IV congestive heart failure, history of acidosis
                   of any type, known kidney injury or disease, alcoholic liver disease or habitual
                   intake of 3 or more alcoholic beverages per day.
      
                -  Known pregnancy or lactating female patients.
      
                -  Known allergic reactions to components of metformin.
      
                -  Prior invasive malignancy within the past year (in remission, without evidence for
                   current active disease and without maintenance therapy). Except non-melanomatous skin
                   cancer, non-invasive carcinoma in-situ of the breast, oral cavity or cervix.
      
                -  Known acquired immune deficiency syndrome.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Loco regional progression-free survival rate
      Time Frame:1 year after start of treatment
      Safety Issue:
      Description:(LPFS)

      Secondary Outcome Measures

      Measure:Overall survival
      Time Frame:time until death; assessed up to 60 months after treatment start
      Safety Issue:
      Description:(OS)
      Measure:Progression-free survival
      Time Frame:earliest date of disease progression (local or distant), assessed up to 24 months after treatment start
      Safety Issue:
      Description:(PFS)

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Ethisch Comité, UZA

      Trial Keywords

      • Tumor Hypoxia
      • Metformin
      • Radiotherapy

      Last Updated

      November 18, 2019