Neoadjuvant FOLFOX Therapy With Short Course Radiation and Active Surveillance in Locally Advanced Rectal Cancer
Condition: Advanced Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: FOLFOX
Intervention description: Patients treated on protocol will be treated with modified FOLFOX. Patients will receive 10 cycles of FOLFOX, administered every other week. FOLFOX will be given on day 1 of each cycle.
Patients will receive oxaliplatin 85 mg/m² IV over 120 minutes, leucovorin 400 mg/m² IV over 120 minutes, 5-FU 400 mg/m² IVP followed by 5-FU 2400 mg/m² infuse over 46 hours.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced rectal cancer; FOLFOX (fluorouracil, leucovorin, oxaliplatin)

Summary:

      The purpose of this study is to evaluate the treatment of patients with locally advanced
      rectal cancer for complete response to neoadjuvant chemotherapy without the use of radiation
      and surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants must be >18 years old at time of diagnosis

          2. Histologically confirmed adenocarcinoma of the rectum from biopsy, defined as
             adenocarcinoma <15 cm from the anal verge

          3. Clinical staging including T3N0 tumors, or T1-3 with N1-2a disease

          4. Patients with lower rectal cancer deemed by surgery to not be candidates for sphincter
             sparing surgery are eligible to participate

          5. There must be no evidence of metastatic disease any time prior to initiation of study

          6. Rectal tumors must be determined as likely requiring total mesorectal excision (TME)

          7. Participant must be treatment naïve for rectal cancer, with no prior radiation
             chemotherapy, radiation, or surgery for specific rectal cancer

          8. No history of prior pelvic radiation

          9. No prior administration of platinum agents

         10. No active infections requiring intravenous antibiotics

         11. No additional active malignancy

         12. No prior treatment of any malignancy within the past 3 years

         13. Baseline lab work must meet the following parameters:

               1. Absolute neutrophil count (ANC)>1500/mm3

               2. Platelet count>100,000/mm3

               3. Hemoglobin>8.0 g/dL

               4. Total bilirubin and creatinine < 1.5x upper limit of normal (ULN)

               5. AST and ALT < 3x ULN

         14. Women of childbearing potential (WCBP) will be defined as those biologically capable
             of becoming pregnant. WCBP must be negative for pregnancy testing (urine or blood) and
             agree to use effective contraception. Viable contraception should be used after trial
             screening, before initiation of chemotherapy, and throughout the duration of active
             treatment in the study.

         15. Participants must be read and explained the purposes of the study, and sign a
             statement of informed consent prior to participation. Those who do not read or
             understand English are eligible and may be consented according to institutional
             federal regulations.

        Exclusion Criteria:

          1. Recurrent or refractory rectal adenocarcinoma

          2. T1N0, T2N0, T4a, T4b, or N2b tumors

          3. Any evidence of metastatic disease

          4. Primary unresectable rectal cancer. A tumor will be considered unresectable when
             invading adjacent organs such that an en bloc resection cannot achieve negative
             margins

          5. Patients with threatened margins, defined as tumor <1 mm from circumferential
             resection margins or mesorectal fascia

          6. Patients unable to undergo MRI imaging

          7. Patient with a history of any arterial thrombotic event within the past 6 months. This
             includes angina, myocardial infarction, transient ischemic attack, or cerebral
             vascular accident.

          8. Patients with history of venous thrombotic episodes such as deep vein thrombosis,
             pulmonary embolus occurring more than 6 months prior to enrollment may be considered
             for protocol participation, provided they are on stable doses of anticoagulant
             therapy. Patients who are anticoagulated for atrial fibrillation or other conditions
             may participate only if on stable doses of anticoagulant therapy.

          9. Patients with cardiovascular, hepatic, or renal systemic diseases that would preclude
             use of chemotherapy

         10. Peripheral neuropathy>grade 1 by Common Terminology Criteria for Adverse Events, or
             CTCAEa

         11. The patient must not be on any clinical trials involving other experimental therapies
             before or during study treatment

         12. Women who are currently pregnant or breast-feeding

         13. Men and women expecting to father/conceive children

         14. Patients with any other concord medical or psychiatric condition which were deemed
             inappropriate for entry into the study per the investigator.

         15. History of other invasive malignancy within the past 3 years, except for adequately
             treated non-melanoma skin cancer, ductal carcinoma in situ, bladder carcinoma in situ
             or carcinoma in situ of the cervix.

        aCTCAE version 5.0 from Department of Health and Human Services