Organ Preservation Program Using Short-Course Radiation & FOLFOXIRI in Rectal Cancer

Prior treatment

• 1.Prior pelvic RT or chemotherapy for rectal cancer.
• 3.Use of other investigational agents.
• 7.Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. (This applies to women who have experienced menarche and have not undergone successful surgical sterilization or are not postmenopausal).
  • Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, known HIV-positive patients with detectable viral loads and/or receiving combination anti-retroviral therapy are excluded from the study.
  • \- 8.Primary unresectable rectal cancer (tumor invading adjacent organs and en bloc resection will not achieve negative margins).

Other illness

• 2.Upper T2N0 rectal cancers eligible for sphincter-preservation surgery
• 4.Ongoing or active infections requiring systemic antibiotic treatment or uncontrolled intercurrent illness including but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• 6.Known hypersensitivity to 5-FU compounds.

Age

• 5.Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Patients with any previous malignancy without evidence of disease for \>3 years will be allowed to enter the trial.

• 1\. Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of rectum requiring total mesorectal excision as deemed by multidisciplinary evaluation
• 2.At least 18 years of age
• 3.For women of childbearing potential or who are not postmenopausal (see Appendix B for Definition of Menopausal Status), a negative urine or serum pregnancy test must be done. Also, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for up to 4 weeks following the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• 4.ECOG 0, 1, or 2
• 5.Ability to understand and the willingness to personally sign the written IRB approved informed consent document.
• 6.Patients must have acceptable organ and marrow function as defined below:
  • Absolute neutrophil count (ANC) \>1,500/uL
  • Hg \> 8.0 g/dL; if blood transfusion is performed for achieving adequate hemoglobin level, the level should stay above goal for at least 1 week after transfusion
  • Platelets \>100,000/uL
  • Total bilirubin \<1.5X normal institutional limits
  • aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT)(SGPT) \< 3X upper limit of normal
  • Creatinine \<1.5X upper limit of normal or creatinine clearance (CrCL)\>50 by Cockcroft-Gault
• 7 Clinical stage \>T2N0 or low T2N0 rectal cancer (AJCC, 8th ed.) including no metastases based on the following diagnostic workup:
  • General history and physical examination with DRE (if deemed appropriate by treating physician) within 45 days prior to enrollment
  • Sigmoidoscopy within 90 days prior to enrollment
  • The following imaging studies are required within 45 days prior to enrollment:
• CT chest/abdomen/pelvis
• MRI Pelvis