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

Randomized Phase II Trial of Definitive Radiotherapy With or Without metFORMin in Patients With Inoperable Stage III Non-small Cell Lung Cancer

Patrocinadores

Patrocinador principal: Ethisch Comité, UZA

Colaborador: Stand Up To Cancer

Fuente University Hospital, Antwerp
Resumen breve

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.

Descripción detallada

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.

Estado general Recruiting
Fecha de inicio July 30, 2018
Fecha de Terminación July 31, 2021
Fecha de finalización primaria July 31, 2020
Fase Phase 2
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Loco regional progression-free survival rate 1 year after start of treatment
Resultado secundario
Medida Periodo de tiempo
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
Inscripción 135
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: Metformin

Descripción: 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.

Etiqueta de grupo de brazo: C: Interventional arm

Tipo de intervención: Other

Nombre de intervención: No metformin

Descripción: Standard of care without metformin.

Etiqueta de grupo de brazo: B: Control arm

Elegibilidad

Criterios:

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.

Género: All

Edad mínima: 18 Years

Edad máxima: N/A

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
Jan van Meerbeeck, PhD, MD Principal Investigator P.I.
Contacto general

Apellido: Mick van de Wiel, MD

Teléfono: +3238213107

Email: [email protected]

Ubicación
Instalaciones: Estado: Contacto: Copia de seguridad de contactos: University Hospital Antwerp Jan van Meerbeeck, PhD, MD +3238213107 [email protected]
Ubicacion Paises

Belgium

Fecha de verificación

November 2019

Fiesta responsable

Tipo: Sponsor-Investigator

Afiliación del investigador: University Hospital, Antwerp

Nombre completo del investigador: Ethisch Comité, UZA

Título del investigador: Head of Department Thoracic Oncology + Principal Investigator (Prof. Dr. Jan van Meerbeeck)

Palabras clave
Tiene acceso ampliado No
Condición Examinar
Número de brazos 3
Grupo de brazo

Etiqueta: A: Observational arm

Tipo: No Intervention

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

Etiqueta: B: Control arm

Tipo: Other

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

Etiqueta: C: Interventional arm

Tipo: Active Comparator

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

Acrónimo RADFORMIN
Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Descripción del modelo de intervención: 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).

Propósito primario: Treatment

Enmascaramiento: None (Open Label)

Fuente: ClinicalTrials.gov