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

Rectal Cancer Clinical Trial

Official title:

Phase II Study Evaluating the Efficacy of the Combination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02437656
• Other study ID #: METCAP-1404
• Secondary ID: 2014-003687-20
• Status: Completed
• Phase: Phase 2
• First received: May 5, 2015
• Last updated: October 24, 2017
• Start date: May 2015
• Est. completion date: March 2017

Study information

• Verified date: October 2017
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

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

Locations

Country	Name	City	State
France	Centre Marie Curie	Arras
France	Centre Pierre Curie	Beuvry
France	Centre Léonard de Vinci - SARL du pont Saint Vaast	Douai
France	Institut André Dutreix	Dunkerque
France	Centre Hospitalier	Lens
France	Centre Galilée - Hôpital Privé La Louvière	Lille
France	Centre Oscar Lambret	Lille
France	Clinique du Bois - Centre Bourgogne	Lille
France	Centre Gray	Maubeuge
France	Centre Joliot-Curie	St Martin-Boulogne
France	Clinique des Dentellières	Valenciennes

Sponsors (1)

Lead Sponsor	Collaborator
Centre Oscar Lambret

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Sphincter preservation rate and downstaging rate		within 30 days after surgery