Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT04170959
Recruitment Status : Terminated (Loss of external funding)
First Posted : November 20, 2019
Last Update Posted : January 15, 2021
Sponsor:
Collaborator:
Stand Up To Cancer
Information provided by (Responsible Party):
ethisch.comite@uza.be, University Hospital, Antwerp

Tracking Information
First Submitted Date  ICMJE May 24, 2019
First Posted Date  ICMJE November 20, 2019
Last Update Posted Date January 15, 2021
Actual Study Start Date  ICMJE July 30, 2018
Actual Primary Completion Date January 8, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2019)
Loco regional progression-free survival rate [ Time Frame: 1 year after start of treatment ]
(LPFS)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2019)
  • Overall survival [ Time Frame: time until death; assessed up to 60 months after treatment start ]
    (OS)
  • Progression-free survival [ Time Frame: earliest date of disease progression (local or distant), assessed up to 24 months after treatment start ]
    (PFS)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Addition of Metformin to Definitive Radiotherapy in Patients With Stage III NSCLC
Official Title  ICMJE Randomized Phase II Trial of Definitive Radiotherapy With or Without metFORMin in Patients With Inoperable Stage III Non-small Cell Lung Cancer
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Prospective multicentre trial, consisting of an observational lead-in phase and a randomized phase II using a 1:1 ratio. All patients willing to participate will receive definitive radiotherapy either in combination with metformin (arm C) or without metformin (arm B).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: Metformin
    Metformin 500 mg given 14 days before start until the end of radiation therapy. Once daily during the first 7 days, afterwards twice daily until the end of treatment.
  • Other: No metformin
    Standard of care without metformin.
Study Arms  ICMJE
  • No Intervention: A: Observational arm
    Radiotherapy as per standard of care without metformin, no additional biomarkers/imaging will be performed
  • B: Control arm
    Radiotherapy as per standard of care without metformin, with additional biomarkers/imaging
    Intervention: Other: No metformin
  • Active Comparator: C: Interventional arm
    Radiotherapy as per standard of care with metformin, with additional biomarkers/imaging
    Intervention: Drug: Metformin
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 Terminated
Actual Enrollment  ICMJE
 (submitted: January 12, 2021)
3
Original Estimated Enrollment  ICMJE
 (submitted: November 18, 2019)
135
Actual Study Completion Date  ICMJE January 8, 2021
Actual Primary Completion Date January 8, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04170959
Other Study ID Numbers  ICMJE OPM-RADFORMIN-1801
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ethisch.comite@uza.be, University Hospital, Antwerp
Study Sponsor  ICMJE ethisch.comite@uza.be
Collaborators  ICMJE Stand Up To Cancer
Investigators  ICMJE
Principal Investigator: Jan van Meerbeeck, PhD, MD P.I.
PRS Account University Hospital, Antwerp
Verification Date January 2021

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