Neo-Adjuvant FOLFOX for Rectal Carcinoma
Condition: Rectal Neoplasms
MeSH terms: Rectal Neoplasms
Intervention: FOLFOX; total mesorectal excision (TME)
Intervention description: 6 cycles of neo-adjuvant mFOLFOX6; TME will be done 4-6 weeks after 6 cycles of neo-adjuvant FOLFOX.
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      A Phase II open- labeled, prospective study to determine the efficacy of pre-operative
      chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME)
      followed by an additional six cycles of FOLFOX 6.

      The objectives of this study are the following:

        1. The primary endpoint of this trial is pathologic complete response (response rate).

        2. Secondary endpoints will include observation of overall pathologic response rate,
           correlation of pathologic staging with pre-operative ultrasound and pelvic MRI staging,
           as well as observation of toxic side effects, patterns of disease relapse, disease-free
           survival outcomes and overall survival outcomes.
    

Eligibility criteria:

        Inclusion Criteria

          1. Patients must consent to participate in the study and must have signed and dated an
             IRB-approved consent form conforming to federal and institutional guidelines

          2. Patient must have histologically proven adenocarcinoma of the rectum with no distant
             metastases

          3. Tumor stage must be T3N0M0, T1-3 N1M0 assessed by clinical exam, TRUS, MRI and CT.
             Pre-operative evidence of T4, N2 or distal lesions (0-6 cm from anal verge) should
             receive preoperative RT and not be offered this protocol. Any pT4, pN2 or CRM+
             patients should be offered postoperative radiation

          4. The proximal border of the tumor must be at or below 12 centimeters of the anal verge
             by proctoscopic examination

          5. The distal border of the tumor must be at or above 6 cm from the anal verge on
             preoperative proctoscopy with the patient in the left lateral decubitus position

          6. Patient must have had no prior chemotherapy or pelvic irradiation

          7. Karnofsky performance status of 60 or greater; ECOG performance status 0-1

          8. Patients should be age 18 years and older

          9. Pretreatment absolute neutrophil count >= 1000/mm3 and platelets >= 100,000/mm3

         10. Serum creatinine <= 1.5 x ULN; bilirubin <= 1.5 x ULN; ALT<= 2.5 x ULN

        Exclusion Criteria

          1. Patients can not be receiving any other investigational agents

          2. Patients with known metastases will be excluded from the study

          3. Patients with history of significant neuropathy or current symptoms of neuropathy

          4. Patients with history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to oxaliplatin or 5-FU or leucovorin

          5. Patients with uncontrolled intercurrent illness not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          6. Pregnant women are excluded from this study because oxaliplatin and 5-FU/LV are agents
             with the potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with oxaliplatin and 5-FU/LV, breastfeeding should be
             discontinued if the mother is treated with these agents

          7. HIV positive patients

          8. Patients with serious comorbid disease which prevents delivery of full treatment
             including psychiatric disorders and cardiopulmonary disease

          9. No history within the past 5 years of a cancer diagnosis except for non-melanomatous
             skin cancers or in situ cervix carcinoma

         10. Patients with clinically significant peripheral neuropathy at the time of start of
             treatment (defined in the NCI Common Terminology Criteria for Adverse Events Version
             3[CTCAE v3.0] as grade 2 or greater neurosensory or neuromotor toxicity