Colorectal Cancer
Conditions
Keywords
rectal cancer, adenocarcinoma of the rectum
Brief summary
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
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.
Interventions
PROCEDUREOpen laparotomy and rectal resection
Patients undergo open laparotomy and rectal resection.
Patients undergo laparoscopic-assisted rectal resection.
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | At time of Surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Completeness of Total Mesorectal Excision (Complete or Nearly Complete) | At time of surgery | 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. |
| Circumferential Margin > 1 mm | At time of surgery | 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. |
| Length of Stay | Two weeks post-surgery | The mean number of days required post-surgery to the when the patient was released from the hospital was calculated. |
| Use of Pain Medication | Two weeks post-surgery | The number of days patients received parenteral narcotics post-surgery were counted. |
| Operative Times | During surgery | Open to close operative time. |
| Negative Distal Resected Margin | At time of surgery | 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. |
| 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 | — |
| Disease-free Survival | Up to 2 years post surgery | — |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 239 |
| 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. | 242 |
| Total | 481 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Metastasis | 2 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 16 | 2 |
Baseline characteristics
| Characteristic | Arm 1: Open Laparotomy and Rectal Resection | Arm 2: Laparoscopic-assisted Rectal Resection | Total |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 12.1 | 57.7 years STANDARD_DEVIATION 11.5 | 57.4 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment United States | 239 participants | 242 participants | 481 participants |
| Sex: Female, Male Female | 81 Participants | 86 Participants | 167 Participants |
| Sex: Female, Male Male | 158 Participants | 156 Participants | 314 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 201 / 239 | 207 / 242 |
| serious Total, serious adverse events | 11 / 239 | 10 / 242 |
Outcome results
Primary
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.
Time frame: At time of Surgery
Population: Of the 225 patients that received intervention as randomized in Arm 1: Open laparotomy and rectal resection, 3 patients were excluded from the analysis due to improper consent. All 240 patients from Arm 2 that received intervention as randomized were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Open Laparotomy and Rectal Resection | 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. | 86.9 percentage of participants |
| Arm 2: Laparoscopic-assisted Rectal Resection | 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. | 81.7 percentage of participants |
p-value: 0.41Wilcoxon (Mann-Whitney)
Secondary
Bowel and Stoma Function
Time frame: Up to 5 years post surgery
Secondary
Bowel Function
Time frame: Up to 5 years post surgery
Secondary
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.
Time frame: At time of surgery
Population: Of the 225 patients that received intervention as randomized in Arm 1: Open laparotomy and rectal resection, 3 patients were excluded from the analysis due to improper consent. All 240 patients from Arm 2 that received intervention as randomized were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Open Laparotomy and Rectal Resection | Circumferential Margin > 1 mm | 92.3 percentage of participants |
| Arm 2: Laparoscopic-assisted Rectal Resection | Circumferential Margin > 1 mm | 87.9 percentage of participants |
Secondary
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.
Time frame: At time of surgery
Population: Of the 225 patients that received intervention as randomized in Arm 1: Open laparotomy and rectal resection, 3 patients were excluded from the analysis due to improper consent. All 240 patients from Arm 2 that received intervention as randomized were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Open Laparotomy and Rectal Resection | Completeness of Total Mesorectal Excision (Complete or Nearly Complete) | 95.1 percentage of participants |
| Arm 2: Laparoscopic-assisted Rectal Resection | Completeness of Total Mesorectal Excision (Complete or Nearly Complete) | 92.1 percentage of participants |
Secondary
Disease-free Survival
Time frame: Up to 2 years post surgery
Secondary
Length of Stay
The mean number of days required post-surgery to the when the patient was released from the hospital was calculated.
Time frame: Two weeks post-surgery
Population: Of the 225 patients that received intervention as randomized in Arm 1: Open laparotomy and rectal resection, 3 patients were excluded from the analysis due to improper consent. All 240 patients from Arm 2 that received intervention as randomized were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Open Laparotomy and Rectal Resection | Length of Stay | 7.0 days | Standard Deviation 3.4 |
| Arm 2: Laparoscopic-assisted Rectal Resection | Length of Stay | 7.3 days | Standard Deviation 5.4 |
Secondary
Local Pelvic Recurrence Rates
Time frame: Up to 2 years post surgery
Secondary
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.
Time frame: At time of surgery
Population: Of the 225 patients that received intervention as randomized in Arm 1: Open laparotomy and rectal resection, 3 patients were excluded from the analysis due to improper consent. All 240 patients from Arm 2 that received intervention as randomized were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Open Laparotomy and Rectal Resection | Negative Distal Resected Margin | 98.2 percentage of participants |
| Arm 2: Laparoscopic-assisted Rectal Resection | Negative Distal Resected Margin | 98.3 percentage of participants |
Secondary
Operative Times
Open to close operative time.
Time frame: During surgery
Population: Of the 225 patients that received intervention as randomized in Arm 1: Open laparotomy and rectal resection, 3 patients were excluded from the analysis due to improper consent. All 240 patients from Arm 2 that received intervention as randomized were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Open Laparotomy and Rectal Resection | Operative Times | 220.6 minutes | Standard Deviation 92.4 |
| Arm 2: Laparoscopic-assisted Rectal Resection | Operative Times | 266.2 minutes | Standard Deviation 101.9 |
Secondary
Overall Survival
Time frame: Up to 5 years post surgery
Secondary
Quality of Life and Sexual Function
Time frame: Up to 5 years post surgery
Secondary
Use of Pain Medication
The number of days patients received parenteral narcotics post-surgery were counted.
Time frame: Two weeks post-surgery
Population: Of the 225 patients that received intervention as randomized in Arm 1: Open laparotomy and rectal resection, 3 patients were excluded from the analysis due to improper consent. All 240 patients from Arm 2 that received intervention as randomized were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Open Laparotomy and Rectal Resection | Use of Pain Medication | 4.2 days | Standard Deviation 2.8 |
| Arm 2: Laparoscopic-assisted Rectal Resection | Use of Pain Medication | 4.2 days | Standard Deviation 3.9 |