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

Study Overview
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Brief Summary
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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.

Detailed Description
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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: To assess patient-related benefit of laparoscopic-assisted resection for rectal cancer vs. open rectal resection (blood loss, length of stay, pain medicine utilization) To assess disease free survival and local pelvic recurrence at two years. 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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Procedure: Open laparotomy and rectal resection
* Procedure: Laparoscopic-assisted rectal resection


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: Histologic diagnosis of adenocarcinoma of the rectum (≤ 12 cm from the anal verge) 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. Completion of pre-operative 5FU based chemotherapy and/or radiation therapy. Capecitabine may be substituted for 5FU. Age ≥ 18 years ECOG (Zubrod) Performance Status ≤ 2 Body Mass Index (BMI) ≤ 34 No evidence of conditions that would preclude use of a laparoscopic approach (eg, multiple previous major laparotomies, severe adhesions) 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. No concurrent or previous invasive pelvic malignancy (cervical, uterine and rectal) within five years prior to registration 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Open laparotomy and rectal resection<br>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<br>* Patients undergo open laparotomy and rectal resection.<br>|
| Experimental: Arm 2: Laparoscopic-assisted rectal resection<br>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<br>* Patients undergo laparoscopic-assisted rectal resection.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, adenocarcinoma of the rectum