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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Metformin Other: No metformin Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
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
Official Title: Randomized Phase II Trial of Definitive Radiotherapy With or Without metFORMin in Patients With Inoperable Stage III Non-small Cell Lung Cancer
Actual Study Start Date : July 30, 2018
Actual Primary Completion Date : January 8, 2021
Actual Study Completion Date : January 8, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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
 Other: No metformin
Standard of care without metformin.
Active Comparator: C: Interventional arm
Radiotherapy as per standard of care with metformin, with additional biomarkers/imaging
 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.


Outcome Measures
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Primary Outcome Measures :
  1. Loco regional progression-free survival rate [ Time Frame: 1 year after start of treatment ]
    (LPFS)


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: time until death; assessed up to 60 months after treatment start ]
    (OS)

  2. Progression-free survival [ Time Frame: earliest date of disease progression (local or distant), assessed up to 24 months after treatment start ]
    (PFS)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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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): NCT04170959


Locations
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Belgium
University Hospital Antwerp
Edegem, Antwerp, Belgium, 2650
Sponsors and Collaborators
ethisch.comite@uza.be
Stand Up To Cancer
Investigators
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Principal Investigator: Jan van Meerbeeck, PhD, MD P.I.
More Information
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Responsible Party: ethisch.comite@uza.be, Head of Department Thoracic Oncology + Principal Investigator (Prof. Dr. Jan van Meerbeeck), University Hospital, Antwerp
ClinicalTrials.gov Identifier: NCT04170959    
Other Study ID Numbers: OPM-RADFORMIN-1801
First Posted: November 20, 2019    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021

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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
Keywords provided by ethisch.comite@uza.be, University Hospital, Antwerp:
Tumor Hypoxia
Metformin
Radiotherapy
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs