Neoadjuvant FOLFOX Therapy With Short Course Radiation and Active Surveillance in Locally Advanced Rectal Cancer

Neoadjuvant FOLFOX Therapy With Short Course Radiation and Active Surveillance in Locally Advanced Rectal Cancer: A Phase II Study

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Rectal Cancer
• Intervention / Treatment: Drug: FOLFOX

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14642
      • University of Rochester, James P. Wilmot Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: FOLFOX; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With a Complete Clinical Response.	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Survival	Will be measured by physical exams	5 years
Proportion of Patients With Survival	Will be measured by laboratory testing	5 years
Proportion of Patients With Survival	Will be measured by proctoscopy	5 years
Proportion of Patients With Survival	Will be measured by sigmoidoscopy	5 years

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Richard Dunne, University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2019
• Primary Completion (Actual): June 1, 2022
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Advanced rectal cancer; FOLFOX (fluorouracil, leucovorin, oxaliplatin)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: UGIC18095

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No