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

NCT ID: NCT02437656

Last Updated: 2017-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2017-03-31

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.

Detailed Description

Patients eligible for the trial and having signed their consent to participate will undergo a dosimetric scan at baseline. 48 hours later (minimum), a Metformin therapy will be started at a dosage of 850 mg 2 times / day ( = 1700 mg / day). Seven days later (minimum) and up to 48 hours before surgery, the dosage of Metformin will be increased to 850 mg 3 times / day ( = 2550 mg / day). This very same day (J10), patients will start a radiochemotherapy. For 5 weeks, 5 days out of 7, patients will receive 800 mg/m² of Capecitabine 2 times / day (on morning and evening) ( = 1600 mg / m² / day) and a 3D irradiation or an Intensity-Modulated Radiation Therapy (IMRT) of a total dose of 50 Gy (5 sessions of 2 Gy per week). 6 to 8 weeks after completion of the chemoradiotherapy, surgery will be scheduled. It will consist of a tumor resection with total resection of the meso rectum.

Prior to the start of treatment, patients will have a clinical and a paraclinical examination and will undergo a laboratory examination. Once a week during the radiochemotherapy, patients will have a clinical examination and will undergo a laboratory examination. Three weeks after the end of the radiochemotherapy, patients will have a clinical examination. Before surgery, patients will have a clinical and a paraclinical examination. Finally, at the end of the study, patients will have a clinical examination.

Conditions

Rectal Cancer

Keywords

Radiochemotherapy; Metformin; Rectal cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin treatment

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)

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

J3 - J10 (7 days minimum) : 850 mg 2 times / day

J10 - 48h before surgery : 850 mg 3 times / day

Interventions

Metformin

J3 - J10 (7 days minimum) : 850 mg 2 times / day

J10 - 48h before surgery : 850 mg 3 times / day

Intervention Type: DRUG

Other Intervention Names

Glucophage; Diabamyl; Stagid

Eligibility Criteria

Inclusion Criteria

1. Patient with an adenocarcinoma of the low or middle rectum.

2. T3 or T4 stage (T evaluated by MRI and / or echo-endoscopy).

3. Absence of distant metastasis.

4. Patient requiring a radiochemotherapy.

5. Correct hematological conditions : Neutrophils ≥ 1500 G / L, platelets ≥ 100 000 G / L.

6. Age ≥ 18 years

7. Performance status (WHO) ≤ 2

8. Lactatemia ≤ Higher standard of the sampling laboratory.

9. For women of childbearing age, a contraceptive method is mandatory for the entire duration of the study.

Exclusion Criteria

1. Other histologies such as squamous cell carcinoma, neuroendocrine tumors, melanomas, etc.

2. History of lactic acidosis.

3. Any diabetes (According to the WHO definition : fasting plasma glucose (FPG) > 1.26 g / L-1).

4. Ongoing antidiabetic treatment such as

• Biguanides, hypoglycemic sulfamides, glinides, GLP-1 analogue, gliptins, alpha-glucosidase inhibitors
• Insulin or insulin analogues

5. Hypersensitivity to capecitabine or to any of the excipients or to fluorouracil.

6. History of severe and unexpected reactions to a fluoropyrimidine therapy.

7. Patient with known deficiency to the dihydropyrimidine dehydrogenase (DPD).

8. Hypersensitivity to metformin or to any of the excipients.

9. Renal failure or impaired renal function (creatinine clearance < 60 ml / min).

10. Severe infection.

11. Acute or chronic disease which may cause tissue hypoxia such as heart or respiratory failure or recent myocardial infarction (< 6 months).

12. Hepatic insufficiency, acute alcohol intoxication, alcoholism.

13. Psychiatric inability to give consent.

14. Contraindication to radiation therapy and/or chemotherapy.

15. Treatment with sorivudine or its chemically related analogues, such as brivudine.

16. Patient under tutorship or guardianship.

17. Pregnant or breastfeeding women.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Oscar Lambret

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier MIRABEL, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Oscar Lambret

Locations

Centre Marie Curie

Arras, , France

Centre Pierre Curie

Beuvry, , France

Centre Léonard de Vinci - SARL du pont Saint Vaast

Douai, , France

Institut André Dutreix

Dunkirk, , France

Centre Hospitalier

Lens, , France

Clinique du Bois - Centre Bourgogne

Lille, , France

Centre Oscar Lambret

Lille, , France

Centre Galilée - Hôpital Privé La Louvière

Lille, , France

Centre Gray

Maubeuge, , France

Centre Joliot-Curie

Saint-Martin-Boulogne, , France

Clinique des Dentellières

Valenciennes, , France

Countries

France

Other Identifiers

2014-003687-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

METCAP-1404

Identifier Type: -

Identifier Source: org_study_id