Laparoscopic-Assisted Resection or Open Resection in Treating Patients With Rectal Cancer

A Phase III Prospective Randomized Trial Comparing Laparoscopic-Assisted Resection Versus Open Resection for Rectal Cancer

This study is being done to compare two types of surgery currently used for rectal cancer. The two types of surgery are laparoscopic-assisted rectal resection and open laparotomy rectal resection. Although laparoscopic-assisted rectal resection is being used for rectal cancer in some medical centers, the effectiveness of this type of surgery compared to open surgery is unknown. The study will compare the safety and effectiveness of the surgeries, recovery from surgery in the hospital, overall recovery from surgery and cancer outcome.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Open laparotomy and rectal resection; Procedure: Laparoscopic-assisted rectal resection

Detailed Description

This is a multicenter study. Patients eligible for this trial will have completed 5FU based neoadjuvant chemotherapy/radiation therapy per the institution's standard of care or IRB approved clinical trial. Patients may be registered/randomized anytime after completion of neoadjuvant therapy, but surgery must occur within 4-12 weeks (28-84 days) after completion of neoadjuvant therapy. Patients are stratified according to the site of the primary tumor (high, middle or low rectum), registering surgeon, and planned operative procedure (low anterior resection or abdominal perineal resection). Patients are randomized to 1 of 2 treatment arms. Please see the arms section for more details. The primary and secondary objectives are listed below.

Primary Objective:

To test the hypothesis that laparoscopic-assisted resection for rectal cancer is not inferior to open rectal resection, based on a composite primary endpoint of oncologic factors which are indicative of a safe and feasible operation.

Secondary Objectives:

1. To assess patient-related benefit of laparoscopic-assisted resection for rectal cancer vs.

   open rectal resection (blood loss, length of stay, pain medicine utilization)

2. To assess disease free survival and local pelvic recurrence at two years.
3. To assess quality of life, sexual function, bowel and stoma function at scheduled time points throughout the trial.

Patients will be evaluated after surgery to determine the need for subsequent care based on the final pathology. Patients should not start treatment on any other investigative trial involving intervention or invasive diagnostic procedures ≤ 30 days following surgery to enable a complete evaluation of post-operative adverse events and complications occurring within 30 days of surgery. Patients are followed periodically for up to 5 years post surgery.

• Study Type: Interventional
• Enrollment (Actual): 486
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital at Providence Health Care - Vancouver
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Hospital - Charlton Campus
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • California
    • Concord, California, United States, 94524-4110
      • Cancer Care Center at John Muir Health - Concord Campus
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Medical Center - Los Angeles
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center - California Campus
    • Walnut Creek, California, United States, 94598
      • John Muir/Mt. Diablo Comprehensive Cancer Center
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida - Weston
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Evanston, Illinois, United States, 60201-1781
      • Evanston Hospital
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Clarian North Medical Center
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • William N. Wishard Memorial Hospital
    • Indianapolis, Indiana, United States, 46202
      • Veterans Affairs Medical Center - Indianapolis
    • Mooresville, Indiana, United States, 46158
      • Kendrick Regional Center for Colon and Rectal Care - Mooresville
  • Iowa
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Medical Center - Burlington
  • Michigan
    • Grand Rapids, Michigan, United States, 49506
      • Blodgett Hospital at Spectrum Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Boone Hospital Center
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Overlook Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • Stony Brook, New York, United States, 11794-9446
      • Stony Brook University Cancer Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73142
      • INTEGRIS Cancer Institute of Oklahoma - Proton Campus
  • Oregon
    • Portland, Oregon, United States, 97213-2967
      • Providence Cancer Center at Providence Portland Medical Center
  • Pennsylvania
    • Monroeville, Pennsylvania, United States, 15146
      • Forbes Regional Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15224-1791
      • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Eligibility Criteria:

1. Histologic diagnosis of adenocarcinoma of the rectum (≤ 12 cm from the anal verge)
2. T3, N0, M0, T1-3, N1-2, M0 disease as determined by pre-neoadjuvant therapy CT scans and pelvic MRI or transrectal ultrasound. Patients with T4 disease are not eligible.
3. Completion of pre-operative 5FU based chemotherapy and/or radiation therapy. Capecitabine may be substituted for 5FU.
4. Age ≥ 18 years
5. ECOG (Zubrod) Performance Status ≤ 2
6. Body Mass Index (BMI) ≤ 34
7. No evidence of conditions that would preclude use of a laparoscopic approach (eg, multiple previous major laparotomies, severe adhesions)

8. No systemic disease (cardiovascular, renal, hepatic) that would preclude surgery. No other severe incapacitating disease:

   • ASA IV: A patient with severe systemic disease that is a constant threat to life. OR
   • ASA V: A moribund patient who is not expected to survive without the operation.
9. No concurrent or previous invasive pelvic malignancy (cervical, uterine and rectal) within five years prior to registration
10. No history of psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.

NOTE: Incompetent patients are not eligible for this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Open laparotomy and rectal resection; Patients undergo open laparotomy and rectal resection. The standard form of surgery is open laparotomy rectal resection. During open laparotomy, the surgeon makes a large incision or cut in the abdomen, and goes in through that cut to remove the tumor and lymph nodes from the rectum.	Procedure: Open laparotomy and rectal resection; Patients undergo open laparotomy and rectal resection.
Experimental: Arm 2: Laparoscopic-assisted rectal resection; Patients undergo laparoscopic-assisted rectal resection. Laparoscopic-assisted rectal resection is performed using small instruments on long handles introduced into the abdomen through small ports called trocars in 3 - 6 positions on the abdomen through incisions measuring 5 -10 mm, under the guidance of a video camera. The abdominal wall is held up with carbon dioxide under pressure. The piece of bowel or intestine is removed through another incision (about 8 centimeters), and the ends of the intestine are reconnected to provide normal bowel function.	Procedure: Laparoscopic-assisted rectal resection; Patients undergo laparoscopic-assisted rectal resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparing Laparoscopic-assisted Resection to Open Rectal Resection for Rectal Cancer as Measured by the Percentage of Patients With Successful Resection Based on Pathological Evaluation.	The primary endpoint will be a composite endpoint of oncologic factors which are indicative of an adequate surgical resection based on pathologic evaluation. Primary endpoint parameters: Circumferential margin > 1 mm; Negative distal margin; Completeness of total mesorectal excision (TME) A complete TME is a rectal resection specimen that has an intact mesorectum and covering peritoneal envelope all the way to the level of rectal transection with no coning in of the mesorectum above the point of transection. The surface of the peritoneal covering should be smooth and shiny with no defects exposing the underlying fat. All three criteria must be met for a resection to be deemed adequate. Laparoscopic-assisted resection will be compared to Open rectal resection to determine if it is non-inferior.	At time of Surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completeness of Total Mesorectal Excision (Complete or Nearly Complete)	Complete total mesorectal excision was defined as a rectal resection specimen having smooth surface of mesorectal fascia with all fat contained in the enveloping fascia to a level 5 cm below the tumor for tumor-specific total mesorectal excision for upper rectal cancer, or the entire mesorectal envelope present for low rectal cancer. Nearly complete was defined as a rectal resection specimen having the mesorectal envelope intact except for defects no more than 5 mm deep, with no loss of mesorectal fat. The percentage of patients with complete or nearly complete mesorectal excision was calculated along with the binomial 95% CI.	At time of surgery
Negative Distal Resected Margin	The percentage of patients with negative distal margin (>1 mm between the closest tumor to the cut edge of the tissue) was calculated along with binomial 95% confidence intervals.	At time of surgery
Circumferential Margin > 1 mm	The distance between the closest tumor to the cut edge of the tissue was measure post-resection. The percentage of patients with >1mm between the closest tumor to the cut edge of the tissue was calculated with a binomial 95% confidence interval.	At time of surgery
Length of Stay	The mean number of days required post-surgery to the when the patient was released from the hospital was calculated.	Two weeks post-surgery
Use of Pain Medication	The number of days patients received parenteral narcotics post-surgery were counted.	Two weeks post-surgery
Operative Times	Open to close operative time.	During surgery
Disease-free Survival		Up to 2 years post surgery
Local Pelvic Recurrence Rates		Up to 2 years post surgery
Overall Survival		Up to 5 years post surgery
Quality of Life and Sexual Function		Up to 5 years post surgery
Bowel Function		Up to 5 years post surgery
Bowel and Stoma Function		Up to 5 years post surgery

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: James W. Fleshman, MD, Baylor Health

Publications and helpful links

General Publications

• Fleshman J, Branda M, Sargent DJ, Boller AM, George V, Abbas M, Peters WR Jr, Maun D, Chang G, Herline A, Fichera A, Mutch M, Wexner S, Whiteford M, Marks J, Birnbaum E, Margolin D, Larson D, Marcello P, Posner M, Read T, Monson J, Wren SM, Pisters PW, Nelson H. Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial. JAMA. 2015 Oct 6;314(13):1346-55. doi: 10.1001/jama.2015.10529.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2008
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: July 31, 2008
• First Submitted That Met QC Criteria: July 31, 2008
• First Posted (Estimate): August 1, 2008

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; rectal cancer
• 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: ACOSOG-Z6051; U10CA076001 (U.S. NIH Grant/Contract); NCI-2009-00350 (Other Identifier: NCI Clinical Trial Reporting Office); CDR0000601816 (Registry Identifier: NCI Physician Data Query)