Esophageal Carcinoma
Conditions
Brief summary
This randomized phase II trial studies how well botulinum toxin type A works in preventing complication after surgery in patients with esophageal cancer. Botulinum toxin type A may cause less complications of nausea and vomiting after surgery.
Detailed description
PRIMARY OBJECTIVES: I. Determine if intra-pyloric botulinum toxin type A (botulinum toxin) injection (Botox) during a minimally invasive esophagectomy decreases postoperative occurrence of delayed gastric emptying. SECONDARY OBJECTIVES: I. Determine if intra-pyloric botulinum toxin injection during a minimally invasive esophagectomy reduces the number of repeat procedures for delayed gastric emptying within 90 days. II. Determine if intra-pyloric botulinum toxin injection during a minimally invasive esophagectomy decreases time to oral intake meeting 100% of nutritional requirements. III. Determine if intra-pyloric botulinum toxin injection during a minimally invasive esophagectomy reduces the incidence of pulmonary complications directly related to delayed gastric emptying. IV. Determine if intra-pyloric botulinum toxin injection during a minimally invasive esophagectomy reduces hospital length of stay related to delayed gastric emptying. V. Determine if intra-pyloric botulinum toxin injection during a minimally invasive esophagectomy increases patient quality of life. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive botulinum toxin type A injection intramuscularly (IM) while undergoing standard minimally invasive esophagectomy. ARM II: Patients undergo standard minimally invasive esophagectomy. After completion of study treatment, patients are followed up at 2, 3-4, and 6-8 weeks, and at 90 days.
Interventions
BIOLOGICALBotulinum Toxin Type A
Given IM
PROCEDUREEsophagectomy
Undergo esophagectomy
OTHERQuality-of-Life Assessment
Ancillary studies
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Esophageal carcinoma, undergoing minimally invasive esophagectomy with intrathoracic anastomosis * Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Exclusion criteria
* Patients who have a history of gastrointestinal dysmotility or functional gastroparesis, including diabetic gastroparesis, central and peripheral nervous system disorders, renal failure, medication side effects, including chronic dependence of promotility agents, anticholinergic antispasmodic agents, or chronic narcotic use over 2 years due to non-cancer causes * Patients who have a history of previous gastric or duodenal surgery * Patients who have a history of duodenal ulcer or duodenal fibrosis * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Allergy to botulinum toxin and/or egg * Pregnant or nursing female participants * Unwilling or unable to follow protocol requirements * Any condition which in the investigator's opinion deems the participant an unsuitable candidate for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delayed Gastric Emptying Assessed Radiographically by Nuclear Medicine Emptying Study | Up to day 21 | Will be assessed using the intent-to-treat principle and a one-sided Cochran-Mantel-Haenszel (CMH) test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal and Nutritional Status Including Days to Resumption of Oral Feeding as Assessed by Dietician | Up to day 35 | The days to resumption of oral feeding are calculated based on return to a solid diet. Will be compared between treatment arms using the two sided independent-sample, stratified T-test. |
| Hospital Length of Stay Attributed to Delayed Gastric Emptying | Up to 90 days | The total length of stay is calculated as the difference between the date of procedure and date of discharge. Will be compared between treatment arms using the two sided independent-sample, stratified T-test. |
| Delayed Gastric Emptying Assessed Radiographically by Gastrografin Swallow OR CT Esophagram | At day 7 | Delayed gastric emptying assessed Radiographically by Gastrografin Swallow OR CT Esophagram at day 7. Will be compared between treatment arms using the two-sided CMH exact test. |
| Pulmonary Events Directly Related to Delayed Gastric Emptying as Assessed by Operating Surgeon | Up to day 90 | The rate of post-operative pulmonary events will be compared between treatment arms using the two-sided CMH exact test. |
| Quality of Life Score as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 OES18 | Up to day 90 | Will be compared between treatment arms using the two sided independent-sample, stratified T-test. |
| Secondary Procedure Due to Delayed Gastric Emptying | Up to 90 days | The rate of secondary procedures (within 90 days) will be compared between treatment arms using a one-sided CMH exact test. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Botulinum Toxin Type A, Esophagectomy) Patients receive botulinum toxin type A injection IM while undergoing standard minimally invasive esophagectomy.
Botulinum Toxin Type A: Given IM
Esophagectomy: Undergo esophagectomy
Quality-of-Life Assessment: Ancillary studies | 15 |
| Arm II (Esophagectomy) Patients undergo standard minimally invasive esophagectomy.
Esophagectomy: Undergo esophagectomy
Quality-of-Life Assessment: Ancillary studies | 17 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Arm II (Esophagectomy) | Arm I (Botulinum Toxin Type A, Esophagectomy) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 7 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Continuous | 61.2 years STANDARD_DEVIATION 11 | 64.2 years STANDARD_DEVIATION 8 | 62.2 years STANDARD_DEVIATION 9.7 |
| Diabetes Status No | 12 Participants | 11 Participants | 23 Participants |
| Diabetes Status Yes | 5 Participants | 4 Participants | 9 Participants |
| Neoadjuvant Chemotherapy Status No | 1 Participants | 1 Participants | 2 Participants |
| Neoadjuvant Chemotherapy Status Yes | 16 Participants | 14 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 16 Participants | 14 Participants | 30 Participants |
| Region of Enrollment United States | 17 participants | 15 participants | 32 participants |
| Self Reported Smoking Status Current Smoker | 1 Participants | 0 Participants | 1 Participants |
| Self Reported Smoking Status Former Smoker | 16 Participants | 15 Participants | 31 Participants |
| Self Reported Smoking Status Never Smoked | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 17 |
| other Total, other adverse events | 8 / 15 | 10 / 17 |
| serious Total, serious adverse events | 1 / 15 | 2 / 17 |
Outcome results
Primary
Delayed Gastric Emptying Assessed Radiographically by Nuclear Medicine Emptying Study
Will be assessed using the intent-to-treat principle and a one-sided Cochran-Mantel-Haenszel (CMH) test.
Time frame: Up to day 21
Population: In Arm I, 2 patients withdrew prior to assessment of primary and secondary outcomes.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Nuclear Medicine Emptying Study | Delayed Gastric Emptying | 12 Participants |
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Nuclear Medicine Emptying Study | No Delayed Gastric Emptying | 1 Participants |
| Arm II (Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Nuclear Medicine Emptying Study | No Delayed Gastric Emptying | 3 Participants |
| Arm II (Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Nuclear Medicine Emptying Study | Delayed Gastric Emptying | 14 Participants |
p-value: 0.773Cochran-Mantel-Haenszel
Secondary
Delayed Gastric Emptying Assessed Radiographically by Gastrografin Swallow OR CT Esophagram
Delayed gastric emptying assessed Radiographically by Gastrografin Swallow OR CT Esophagram at day 7. Will be compared between treatment arms using the two-sided CMH exact test.
Time frame: At day 7
Population: 2 patients in Arm I withdrew prior to any assessments.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Gastrografin Swallow OR CT Esophagram | Delayed gastric Emptying | 12 Participants |
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Gastrografin Swallow OR CT Esophagram | No Delayed Gastric Emptying | 1 Participants |
| Arm II (Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Gastrografin Swallow OR CT Esophagram | Delayed gastric Emptying | 14 Participants |
| Arm II (Esophagectomy) | Delayed Gastric Emptying Assessed Radiographically by Gastrografin Swallow OR CT Esophagram | No Delayed Gastric Emptying | 3 Participants |
p-value: 0.773Cochran-Mantel-Haenszel
Secondary
Gastrointestinal and Nutritional Status Including Days to Resumption of Oral Feeding as Assessed by Dietician
The days to resumption of oral feeding are calculated based on return to a solid diet. Will be compared between treatment arms using the two sided independent-sample, stratified T-test.
Time frame: Up to day 35
Population: 2 patients in Arm I withdrew prior to study assessments. Data were not captured and is unavailable for 1 patient in Arm I and 4 patients in Arm II.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Gastrointestinal and Nutritional Status Including Days to Resumption of Oral Feeding as Assessed by Dietician | 22.6 days | Standard Deviation 4.7 |
| Arm II (Esophagectomy) | Gastrointestinal and Nutritional Status Including Days to Resumption of Oral Feeding as Assessed by Dietician | 27 days | Standard Deviation 16.2 |
p-value: 0.368t-test, 2 sided
Secondary
Hospital Length of Stay Attributed to Delayed Gastric Emptying
The total length of stay is calculated as the difference between the date of procedure and date of discharge. Will be compared between treatment arms using the two sided independent-sample, stratified T-test.
Time frame: Up to 90 days
Population: 2 participants in arm I withdrew prior to any study assessments. Data were not captured and unavailable for 1 patient in Arm I and 1 patient in Arm II.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Hospital Length of Stay Attributed to Delayed Gastric Emptying | 7.9 days | Standard Deviation 4.2 |
| Arm II (Esophagectomy) | Hospital Length of Stay Attributed to Delayed Gastric Emptying | 8.1 days | Standard Deviation 1.9 |
p-value: 0.987t-test, 2 sided
Secondary
Pulmonary Events Directly Related to Delayed Gastric Emptying as Assessed by Operating Surgeon
The rate of post-operative pulmonary events will be compared between treatment arms using the two-sided CMH exact test.
Time frame: Up to day 90
Population: 2 participants in arm I withdrew prior to any study assessments. Data were not captured and unavailable for 1 patient in Arm I and 1 patient in Arm II.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Pulmonary Events Directly Related to Delayed Gastric Emptying as Assessed by Operating Surgeon | Pulmonary Complication | 3 Participants |
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Pulmonary Events Directly Related to Delayed Gastric Emptying as Assessed by Operating Surgeon | No Pulmonary Complication | 9 Participants |
| Arm II (Esophagectomy) | Pulmonary Events Directly Related to Delayed Gastric Emptying as Assessed by Operating Surgeon | Pulmonary Complication | 3 Participants |
| Arm II (Esophagectomy) | Pulmonary Events Directly Related to Delayed Gastric Emptying as Assessed by Operating Surgeon | No Pulmonary Complication | 13 Participants |
p-value: 1Cochran-Mantel-Haenszel
Secondary
Quality of Life Score as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 OES18
Will be compared between treatment arms using the two sided independent-sample, stratified T-test.
Time frame: Up to day 90
Population: The quality of life data were not captured.
Secondary
Secondary Procedure Due to Delayed Gastric Emptying
The rate of secondary procedures (within 90 days) will be compared between treatment arms using a one-sided CMH exact test.
Time frame: Up to 90 days
Population: 2 participants in arm I withdrew prior to any study assessments. Data were not captured and unavailable for 2 patients in Arm I and 2 patients in Arm II.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Secondary Procedure Due to Delayed Gastric Emptying | Reoperation | 1 Participants |
| Arm I (Botulinum Toxin Type A, Esophagectomy) | Secondary Procedure Due to Delayed Gastric Emptying | No Reoperation | 10 Participants |
| Arm II (Esophagectomy) | Secondary Procedure Due to Delayed Gastric Emptying | Reoperation | 0 Participants |
| Arm II (Esophagectomy) | Secondary Procedure Due to Delayed Gastric Emptying | No Reoperation | 15 Participants |
p-value: 0.423Cochran-Mantel-Haenszel