Combination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer.

NCT02437656 | Completed Phase 2

• 2 other identifiers: METCAP-14042014-003687-20
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 11

Brief Summary

Metformin is an oral antidiabetic of the biguanide class derived from galega officinalis. Historical cohort of patients with diabetes have shown that diabetics on Metformin had a better chance of survival than diabetics not on Metformin. These observations have led to in vitro studies of metformin on cancer cells. It was thus demonstrated that Metformin has anti-proliferative properties. The aim of our study is to evaluate the efficacy of metformin in combination with neoadjuvant radiochemotherapy in the treatment of locally advanced rectal cancer.

Conditions

Rectal Cancer

Keywords

Radiochemotherapy; Metformin; Rectal cancer

Outcome Measures

Primary Outcomes (1)

• The efficacy will be assessed on the operative specimen by the complete histological response rate (absence of tumor cells : pCR).

  within 30 days after surgery

Secondary Outcomes (2)

• Toxicity will be assessed according to NCI-CTCAE v4.0. Grades ≥ 3 related to metformin will be collected by the clinician.

  up to 30 days after the end of the treatments (metformin and radiochemotherapy)

• Sphincter preservation rate and downstaging rate

  within 30 days after surgery

Study Arms (1)

Metformin treatment

EXPERIMENTAL

J1 : dosimetric scan J3 : initiation of the Metformin therapy (at a dosage of 1700 mg / day) J10 : increasing the dose of Metformin (2550 mg / day) + initiation of the radiochemotherapy J44 : end of the radiochemotherapy Between J86 and J100 : surgery (discontinuation of the Metformin therapy 48 hours before surgery)

Drug: Metformin

Interventions

Metformin DRUG

J3 - J10 (7 days minimum) : 850 mg 2 times / day J10 - 48h before surgery : 850 mg 3 times / day

Also known as: Glucophage, Diabamyl, Stagid

Metformin treatment

Eligibility Criteria

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

You may qualify if:

• Patient with an adenocarcinoma of the low or middle rectum.
• T3 or T4 stage (T evaluated by MRI and / or echo-endoscopy).
• Absence of distant metastasis.
• Patient requiring a radiochemotherapy.
• Correct hematological conditions : Neutrophils ≥ 1500 G / L, platelets ≥ 100 000 G / L.
• Age ≥ 18 years
• Performance status (WHO) ≤ 2
• Lactatemia ≤ Higher standard of the sampling laboratory.
• For women of childbearing age, a contraceptive method is mandatory for the entire duration of the study.

You may not qualify if:

• Other histologies such as squamous cell carcinoma, neuroendocrine tumors, melanomas, etc.
• History of lactic acidosis.
• Any diabetes (According to the WHO definition : fasting plasma glucose (FPG) \> 1.26 g / L-1).
• Ongoing antidiabetic treatment such as
• Biguanides, hypoglycemic sulfamides, glinides, GLP-1 analogue, gliptins, alpha-glucosidase inhibitors
• Insulin or insulin analogues
• Hypersensitivity to capecitabine or to any of the excipients or to fluorouracil.
• History of severe and unexpected reactions to a fluoropyrimidine therapy.
• Patient with known deficiency to the dihydropyrimidine dehydrogenase (DPD).
• Hypersensitivity to metformin or to any of the excipients.
• Renal failure or impaired renal function (creatinine clearance \< 60 ml / min).
• Severe infection.
• Acute or chronic disease which may cause tissue hypoxia such as heart or respiratory failure or recent myocardial infarction (\< 6 months).
• Hepatic insufficiency, acute alcohol intoxication, alcoholism.
• Psychiatric inability to give consent.

Sponsors & Collaborators

• Centre Oscar Lambret: lead

Study Sites (11)

Centre Marie Curie

Arras, 62000, France

Location

Centre Pierre Curie

Beuvry, 62880, France

Location

Centre Léonard de Vinci - SARL du pont Saint Vaast

Douai, 59500, France

Location

Institut André Dutreix

Dunkirk, 59240, France

Location

Centre Hospitalier

Lens, 62300, France

Location

Clinique du Bois - Centre Bourgogne

Lille, 59000, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Galilée - Hôpital Privé La Louvière

Lille, 59045, France

Location

Centre Gray

Maubeuge, 59600, France

Location

Centre Joliot-Curie

Saint-Martin-Boulogne, 62200, France

Location

Clinique des Dentellières

Valenciennes, 59300, France

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Xavier MIRABEL, MD

  Centre Oscar Lambret

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 7, 2015
• Study Start: May 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)