- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04170959
The Addition of Metformin to Definitive Radiotherapy in Patients With Stage III NSCLC (RADFORMIN)
January 12, 2021 updated by: ethisch.comite@uza.be
Randomized Phase II Trial of Definitive Radiotherapy With or Without metFORMin in Patients With Inoperable Stage III Non-small Cell Lung Cancer
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
3
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Antwerp
-
Edegem, Antwerp, Belgium, 2650
- University Hospital Antwerp
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: A: Observational arm
Radiotherapy as per standard of care without metformin, no additional biomarkers/imaging will be performed
|
|
Other: B: Control arm
Radiotherapy as per standard of care without metformin, with additional biomarkers/imaging
|
Standard of care without metformin.
|
Active Comparator: C: Interventional arm
Radiotherapy as per standard of care with metformin, with additional biomarkers/imaging
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Loco regional progression-free survival rate
Time Frame: 1 year after start of treatment
|
(LPFS)
|
1 year after start of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: time until death; assessed up to 60 months after treatment start
|
(OS)
|
time until death; assessed up to 60 months after treatment start
|
Progression-free survival
Time Frame: earliest date of disease progression (local or distant), assessed up to 24 months after treatment start
|
(PFS)
|
earliest date of disease progression (local or distant), assessed up to 24 months after treatment start
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Jan van Meerbeeck, PhD, MD, P.I.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 30, 2018
Primary Completion (Actual)
January 8, 2021
Study Completion (Actual)
January 8, 2021
Study Registration Dates
First Submitted
May 24, 2019
First Submitted That Met QC Criteria
November 18, 2019
First Posted (Actual)
November 20, 2019
Study Record Updates
Last Update Posted (Actual)
January 15, 2021
Last Update Submitted That Met QC Criteria
January 12, 2021
Last Verified
January 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- OPM-RADFORMIN-1801
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Carcinoma, Non-Small-Cell Lung
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Bristol-Myers SquibbCompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage I Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung Carcinoma | Non-Squamous Non-Small...United States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Recurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7 | Recurrent Lung Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IA...United States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
M.D. Anderson Cancer CenterActive, not recruitingStage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage II Lung Non-Small Cell Cancer AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7 | Stage I Lung Non-Small Cell Cancer AJCC v7 | Stage...United States
-
National Cancer Institute (NCI)Active, not recruitingLung Non-Squamous Non-Small Cell Carcinoma | Stage IB Lung Non-Small Cell Carcinoma AJCC v7 | Stage II Lung Non-Small Cell Cancer AJCC v7 | Stage IIA Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIB Lung Non-Small Cell Carcinoma AJCC v7 | Stage IIIA Lung Non-Small Cell Cancer AJCC v7United States, Puerto Rico
-
National Cancer Institute (NCI)Active, not recruitingStage IIIA Lung Non-Small Cell Cancer AJCC v7 | Advanced Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IV Lung Non-Small Cell Cancer AJCC v7 | Stage III Lung Non-Small Cell Cancer AJCC...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Society of Thoracic RadiologyActive, not recruitingStage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-Small Cell Lung Cancer | Stage IIIB Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Carcinoma | Stage IIB Non-Small Cell Lung Carcinoma | Stage IA Non-Small Cell Lung Carcinoma | Stage IB Non-Small Cell Lung CarcinomaUnited States
Clinical Trials on No metformin
-
Ottawa Hospital Research InstituteCIHR Canadian HIV Trials NetworkWithdrawn
-
Copenhagen University Hospital at HerlevNot yet recruiting
-
Albert Einstein College of MedicineCompleted
-
Asan Medical CenterHanAll BioPharma Co., Ltd.Completed
-
Anji PharmaSuspendedDiabetes Mellitus, Type 2Spain, United States, Canada, Hungary, Brazil, Czechia, Poland, Bulgaria
-
ShionogiCompleted
-
NuSirt BiopharmaCompletedType 2 Diabetes MellitusUnited States
-
Bristol-Myers SquibbCompletedType 2 Diabetes MellitusSouth Africa, United States, Canada, Puerto Rico, Hungary, Germany, Czechia, Poland, Romania, United Kingdom
-
Charles University, Czech RepublicCompleted