Neoadjuvant FOLFOX Therapy With Short Course Radiation and Active Surveillance in Locally Advanced Rectal Cancer: A Phase II Study
Overview
- Phase
- Phase 2
- Intervention
- FOLFOX
- Conditions
- Advanced Rectal Cancer
- Sponsor
- University of Rochester
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- Proportion of Patients With a Complete Clinical Response.
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief 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.
Detailed Description
These patients will be evaluated for complete clinical response (cCR) after completing 10 cycles of FOLFOX (fluorouracil, leucovorin, oxaliplatin) chemotherapy, with interval analysis after six cycles. Patients who have stable or progressive disease will be treated per discretion of the treating physician following multidisciplinary discussion. Those determined to have partial or complete response will complete full neoadjuvant treatment and undergo close surveillance with watchful waiting for local recurrence without immediate surgery. The primary endpoint of this study will be the rate of cCR, which is to include complete and near complete clinical response, with secondary endpoints of disease free survival (DFS), overall survival (OS), quality of life (QOL), as well as evaluation of safety and toxicity.
Investigators
Richard Dunne
Associate Professor of Hematology/Oncology
University of Rochester
Eligibility Criteria
Inclusion Criteria
- •Participants must be \>18 years old at time of diagnosis
- •Histologically confirmed adenocarcinoma of the rectum from biopsy, defined as adenocarcinoma \<15 cm from the anal verge
- •Clinical staging including T3N0 tumors, or T1-3 with N1-2a disease
- •Patients with lower rectal cancer deemed by surgery to not be candidates for sphincter sparing surgery are eligible to participate
- •There must be no evidence of metastatic disease any time prior to initiation of study
- •Rectal tumors must be determined as likely requiring total mesorectal excision (TME)
- •Participant must be treatment naïve for rectal cancer, with no prior radiation chemotherapy, radiation, or surgery for specific rectal cancer
- •No history of prior pelvic radiation
- •No prior administration of platinum agents
- •No active infections requiring intravenous antibiotics
Exclusion Criteria
- •Recurrent or refractory rectal adenocarcinoma
- •T1N0, T2N0, T4a, T4b, or N2b tumors
- •Any evidence of metastatic disease
- •Primary unresectable rectal cancer. A tumor will be considered unresectable when invading adjacent organs such that an en bloc resection cannot achieve negative margins
- •Patients with threatened margins, defined as tumor \<1 mm from circumferential resection margins or mesorectal fascia
- •Patients unable to undergo MRI imaging
- •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.
- •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.
- •Patients with cardiovascular, hepatic, or renal systemic diseases that would preclude use of chemotherapy
- •Peripheral neuropathy\>grade 1 by Common Terminology Criteria for Adverse Events, or CTCAEa
Arms & Interventions
mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)
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.
Intervention: FOLFOX
Outcomes
Primary Outcomes
Proportion of Patients With a Complete Clinical Response.
Time Frame: 1 year
* A complete response will consist of a digital rectal exam with normal appearing mucosa and sigmoidoscopy/proctoscopy with scarring but no nodularity or ulcerations. * A near complete response will consist of digital rectal exam with smooth or minor mucosal abnormalities, and sigmoidoscopy/proctoscopy with small mucosal abnormalities, or superficial ulceration or erythematous scarring. * Partial response, in our study, will be those tumors read with RECIST version 1.1 criteria with a ≥20% decrease in size without obtaining near or complete response. * Stable disease, in our study, will be those tumors read with RECIST criteria with a \<20% decrease in size without obtaining near or complete response. * Progressive disease will be those tumors with \>20% increase in size by RECIST version 1.1 criteria on imaging.
Secondary Outcomes
- Proportion of Patients With Survival(5 years)