
    slow accrual
  
['rectal neoplasms', 'adenocarcinoma', 'carcinoma']
['capecitabine', 'metformin', 'placebo']

        Inclusion Criteria:

          -  18 years or older;

          -  biopsy proven poorly differentiated carcinoma or adenocarcinoma of the rectum;

          -  lesions located within 12 cm of the anal verge (from colonoscopy assessment);

          -  ability to tolerate oral treatment;

          -  locally advanced tumor, classified by the presence of positive regional lymph nodes or
             primary tumor invasion beyond the serosa (T3 or T4), assessed by MRI;

          -  eligibility for curative surgery (no distant metastasis or invasion of bony structures
             of the pelvis);

          -  Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) 0-2;

          -  adequate hematologic functions (hemoglobin ≥ 10 g / dL [5.6 mmol / L]; neutrophil
             count ≥ 1,500 / mm3 and platelet count ≥ 100,000 / mm3), adequate renal function
             (serum creatinine less than 1.5 times the UNL) and adequate hepatic function
             (bilirubin less than 1.5 times the UNL; aspartate aminotransferase and alanine
             aminotransferase less than 2.5 times the UNL);

        Exclusion Criteria:

          -  known hypersensitivity to metformin or its excipients;

          -  squamous carcinomas of the rectum or anal canal;

          -  chronic treatment with corticosteroids or other immunosuppressive agents;

          -  treatment with oral antidiabetic products;

          -  distant metastasis at diagnosis or tumor invasion of pelvic bone structures that may
             proscribe curative intent surgery;

          -  chronic or acute infections;

          -  use of drugs under study up to four weeks prior to randomization;

          -  pregnant or nursing patients;

          -  prior radiotherapy to the pelvic region;

          -  myocardial infarction up to six months prior to randomization, or uncontrolled
             ischemic heart disease;

          -  congestive heart insufficiency New York Heart Association (NYHA) III-IV.
      