Watchful Waiting for Complete Responders to Therapy in Rectal Cancer

Treatment of T2-T3/NO-N+ Adenocarcinoma of the Rectum by Neoadjuvant Chemotherapy (FOLFOX) Followed by Preoperative Chemo (Fluorouracil / Capecitabine)-Radio Therapy (CRT) With Watchful Waiting for Complete Responders

The purpose of this project is to determine if in a selected group of patients, at higher risk of wound dehiscence and other complications, treatment by local excision and management by a "watchful waiting" or an initial "non-operative management" approach, with an offer of radical resection only to those patients whose tumors demonstrate "regrowth" will maintain acceptable local control and overall survival rate for the whole cohort.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Other: Watchfuf waiting

Detailed Description

This is a prospective registration study of a very limited number of subjects (3-8/year) who have achieved full or near full clinical CR after neo-adjuvant FOLFOX chemotherapy prior to chemo-radiotherapy, but without subsequent surgery, to determine whether a "wait and see" approach will maintain local control while improving quality of life. Patients will undergo standard of care baseline work-up for their disease before being enrolled to the protocol followed by protocol treatment, all standard of care just in reverse order. Patients with less than 1/2 of the rectum being circumferentially involved at diagnosis will also receive additional brachytherapy which will be supported by hospital funded research dollars. Patients will undergo additional testing for study related purposes during the restaging processes such as MRI, endoscopic ultrasound, and will complete an assessment to determine impact on quality of life. Providers that will be conducting the MRI and endoscopic ultrasound have agreed to waive professional fees, as well as the hospital has agreed to waive facility fees that have been incurred while the patient is on study protocol. Patients will follow standard of care guidelines for follow up post-excision if they do not respond to treatment, and modified standard of care guidelines if their are identified as complete responders which will include additional imaging at specific milestones, again waived by providers and facility. Patients on watchful waiting, who recur locally will undergo total mesorectal excision. Patients will not be responsible for any fee incurred that is not considered standard of care.

Patients will be accrued as they present to the Van Elslander and Webber cancer center clinics. They will be enrolled in this arm of the study only if surgical evaluation indicates that surgical resection will extend to include the dentate line if said patients were candidates for local excision. We expect that about 3 patients/year will be eligible.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amr Aref, MD; Phone Number: (313) 647-3100; Email: amr.aref@ascension.org

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Recruiting
      • Ascension St. John Hospital
      • Contact: Amr Aref, MD; Phone Number: 313-647-3100; Email: amr.aref@ascension.org
      • Contact: Karen Forman; Phone Number: 313-343-4974; Email: karen.forman@ascension.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Diagnosis of rectal invasive adenocarcinoma
3. Tumor in the low rectum lying < 4 cm from the anal verge
4. Clinical stage T3/N0-N1M0.
5. Patients with low T2 who will need abdominal perineal resection are also eligible.

Exclusion Criteria:

1. Age less than 18 years
2. Other forms of cancer
3. Tumors >= 4 cm from the anal verge
4. Tumors of other clinical stages than listed above

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: Watchful Waiting; Six cycles of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) will be administered every two weeks according to protocol. After a 3 week recovery period, this will be followed by conventional concurrent radiation and 5FU/capecitabine. Patients will be re-staged two to three weeks after completion of induction FOLFOX therapy to ensure no disease progression. The patients will be re-staged again at least 7-11 weeks post completion of nCRT. Patients with restaging results showing either complete or near complete response, will be allocated to "watchful waiting."

Other: Watchfuf waiting; Careful review of patient response with the hope of avoiding radical surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence free survival	Survival without recurrence of the cancer	three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life using LARS score	Measures of patient comfort and satisfaction	three years

Collaborators and Investigators

• Sponsor: Ascension South East Michigan
• Investigators: Principal Investigator: Amr Aref, MD, Ascension St. John Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2018
• Primary Completion (Estimated): July 9, 2028
• Study Completion (Estimated): July 9, 2029

Study Registration Dates

• First Submitted: August 27, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• 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: 1291129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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