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

Phase 2

Active, not recruiting

• Conditions: Advanced Rectal Cancer
• Interventions: Drug: FOLFOX

• Registration Number: NCT03781323
• Lead Sponsor: University of Rochester

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.

Study Timeline

• Study First Submitted: 2018-12-13
• Study First Submitted QC: 2018-12-17
• Study First Posted: 2018-12-19
• Study Start: 2019-05-03
• Primary Completion: 2022-06-01
• Results First Submitted: 2023-08-16
• Results First Submitted QC: 2023-08-16
• Results First Posted: 2023-09-11
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-13
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
mFOLFOX (5-Fluorouracil Leucovorin Oxaliplatin)	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With a Complete Clinical Response.	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 Outcome Measures

Name	Time	Method
Proportion of Patients With Survival	5 years	Will be measured by sigmoidoscopy

Trial Locations

Locations (2)

University of Rochester; 🇺🇸 Rochester, New York, United States

University of Rochester, James P. Wilmot Cancer Center; 🇺🇸 Rochester, New York, United States