Phase II/III Randomized Multicentre Study Comparing Neoadjuvant Chemoradiotherapy Followed by Consolidation Chemotherapy to Neoadjuvant Chemoradiotherapy Alone in Non-metastatic Rectal Cancer Patients.
This is a Phase II/III randomized study involving non-metastatic rectal cancer patients who are candidates for neoadjuvant chemoradiotherapy. Eligible patients will be randomized between two treatment arms: Experimental arm: Long course CRT is followed by 4 cycles of combination chemotherapy of modified FOLFOX6 or 3 cycles of XELOX and then surgery. After surgery, patients with pT0-2 N0 will not receive adjuvant chemotherapy. Patients with higher pathological stage will receive adjuvant chemotherapy (4 cycles of modified FOLFOX6 or 3 cycles of XELOX). Standard arm: Long course CRT will be followed by surgery 10-12 weeks after the end of CRT. After surgery, patients with pT0-2 N0 will not receive adjuvant chemotherapy. Patients with higher pathological stage will receive adjuvant chemotherapy (8 cycles of modified FOLFOX6 or 6 cycles of XELOX). The study aims to assess the efficacy of consolidation chemotherapy given in the interval between the end of CRT and surgery to allow for early initiation of systemic therapy aiming to decrease distant relapse rate and enhancing pathological response.
• Age ≥ 18 years at diagnosis
• Histopathological diagnosis of rectal adenocarcinoma
• ECOG Performance Status (PS): 0- 2
• Clinical Stage: T2 N1-2, T3N0-2, T4 N0-2 based on pelvic MRI. Lymph node will be considered radiologically positive if: - size (short axis≥ 1cm) and/or - Morphological changes: irregular outlines/ abnormal signal intensity, positive enhancement.
• The standard treatment recommendation of included patients in the absence of a clinical trial would be combined modality neoadjuvant CRT followed by curative intent surgical resection.
• Primary surgeon is planning to perform Total Mesorectal Excision (TME).
• The following laboratory values must be obtained ≤ 28 days prior to registration:
‣ Absolute neutrophil count (ANC) ≥ 1500/mm3
⁃ Platelet count ≥ 100,000/mm3
⁃ Hemoglobin \> 8.0 g/dl (transfusion permitted)
⁃ Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
⁃ SGOT (AST) ≤ 3 x ULN
⁃ SGPT (ALT) ≤ 3 x ULN
⁃ Creatinine ≤1.5 x ULN or Creatinine clearance \> 50ml/minute by Cockcroft-Gault formula.
• Negative pregnancy test ≤ 7 days prior to registration for women of childbearing potential only.
• Patient of child-bearing potential is willing to employ an adequate contraception method
• Provide informed written consent
• Willing to return to the enrolling medical site for all study assessments