Back to resultsCombination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer (METCAP).
Primary Purpose
Rectal Cancer
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Cancer focused on measuring Radiochemotherapy, Metformin, Rectal cancer
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Contraindication to radiation therapy and/or chemotherapy.
- Treatment with sorivudine or its chemically related analogues, such as brivudine.
- Patient under tutorship or guardianship.
- Pregnant or breastfeeding women.
Sites / Locations
- Centre Marie Curie
- Centre Pierre Curie
- Centre Léonard de Vinci - SARL du pont Saint Vaast
- Institut André Dutreix
- Centre Hospitalier
- Clinique du Bois - Centre Bourgogne
- Centre Oscar Lambret
- Centre Galilée - Hôpital Privé La Louvière
- Centre Gray
- Centre Joliot-Curie
- Clinique des Dentellières
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Metformin treatment
Arm Description
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)
Outcomes
Primary Outcome Measures
The efficacy will be assessed on the operative specimen by the complete histological response rate (absence of tumor cells : pCR).
Secondary Outcome Measures
Toxicity will be assessed according to NCI-CTCAE v4.0. Grades ≥ 3 related to metformin will be collected by the clinician.
Sphincter preservation rate and downstaging rate
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02437656
Brief Title
Combination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer (METCAP).
Official Title
Phase II Study Evaluating the Efficacy of the Combination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Oscar Lambret
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Radiochemotherapy, Metformin, Rectal cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metformin treatment
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage, Diabamyl, Stagid
Intervention Description
J3 - J10 (7 days minimum) : 850 mg 2 times / day
J10 - 48h before surgery : 850 mg 3 times / day
Primary Outcome Measure Information:
Title
The efficacy will be assessed on the operative specimen by the complete histological response rate (absence of tumor cells : pCR).
Time Frame
within 30 days after surgery
Secondary Outcome Measure Information:
Title
Toxicity will be assessed according to NCI-CTCAE v4.0. Grades ≥ 3 related to metformin will be collected by the clinician.
Time Frame
up to 30 days after the end of the treatments (metformin and radiochemotherapy)
Title
Sphincter preservation rate and downstaging rate
Time Frame
within 30 days after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Contraindication to radiation therapy and/or chemotherapy.
Treatment with sorivudine or its chemically related analogues, such as brivudine.
Patient under tutorship or guardianship.
Pregnant or breastfeeding women.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xavier MIRABEL, MD
Organizational Affiliation
Centre Oscar Lambret
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Marie Curie
City
Arras
ZIP/Postal Code
62000
Country
France
Facility Name
Centre Pierre Curie
City
Beuvry
ZIP/Postal Code
62880
Country
France
Facility Name
Centre Léonard de Vinci - SARL du pont Saint Vaast
City
Douai
ZIP/Postal Code
59500
Country
France
Facility Name
Institut André Dutreix
City
Dunkerque
ZIP/Postal Code
59240
Country
France
Facility Name
Centre Hospitalier
City
Lens
ZIP/Postal Code
62300
Country
France
Facility Name
Clinique du Bois - Centre Bourgogne
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Centre Galilée - Hôpital Privé La Louvière
City
Lille
ZIP/Postal Code
59045
Country
France
Facility Name
Centre Gray
City
Maubeuge
ZIP/Postal Code
59600
Country
France
Facility Name
Centre Joliot-Curie
City
St Martin-Boulogne
ZIP/Postal Code
62200
Country
France
Facility Name
Clinique des Dentellières
City
Valenciennes
ZIP/Postal Code
59300
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Combination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer (METCAP).
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