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

NCT04170959 | Terminated Phase 2 DMC

• 1 other identifier: OPM-RADFORMIN-1801
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Tumor Hypoxia; Metformin; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Loco regional progression-free survival rate

  (LPFS)

  1 year after start of treatment

Secondary Outcomes (2)

• Overall survival

  time until death; assessed up to 60 months after treatment start

• Progression-free survival

  earliest date of disease progression (local or distant), assessed up to 24 months after treatment start

Study Arms (3)

A: Observational arm

NO INTERVENTION

Radiotherapy as per standard of care without metformin, no additional biomarkers/imaging will be performed

B: Control arm

OTHER

Radiotherapy as per standard of care without metformin, with additional biomarkers/imaging

Other: No metformin

C: Interventional arm

ACTIVE COMPARATOR

Radiotherapy as per standard of care with metformin, with additional biomarkers/imaging

Drug: Metformin

Interventions

Metformin DRUG

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.

C: Interventional arm

No metformin OTHER

Standard of care without metformin.

B: Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• ethisch.comite@uza.be: lead
• Stand Up To Cancer: collaborator

Study Sites (1)

University Hospital Antwerp

Edegem, Antwerp, 2650, Belgium

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Metformin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Jan van Meerbeeck, PhD, MD

  P.I.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Department Thoracic Oncology + Principal Investigator (Prof. Dr. Jan van Meerbeeck)

Model Details: 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).

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: November 20, 2019
• Study Start: July 30, 2018
• Primary Completion: January 8, 2021
• Study Completion: January 8, 2021
• Last Updated: January 15, 2021

Record last verified: 2021-01

Locations

BE (1)