Barrett Esophagus, Early Stage Esophageal Adenocarcinoma
Conditions
Brief summary
This study is being done to see if treatment for esophageal cancer can be done using endoscopy for patients ineligible for surgical or radiological therapy. The standard method of treating this type of cancer is surgical removal of the esophagus. The study will determine if removing just the cancer with endoscopy is enough treatment or if the addition of another treatment called photodynamic therapy (treatment with a red light and a drug called sodium porfimer) is needed.
Detailed description
Participant visit requirements: Screening visit which will last 1 - 2 days, if assigned to photodynamic therapy, there will be a 3 day visit for treatment. Participants must return for a 1 day visit every three months for one year.
Interventions
PROCEDUREEndoscopic Mucosal Resection
Endoscopic mucosal resection at time of endoscopy if indicated.
PROCEDUREPhotodynamic Therapy
Porfimer sodium 2mg/kg
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
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
* Non-recurrent adenocarcinoma in Barrett's Esophagus confirmed by two experienced gastrointestinal pathologists * No evidence of submucosal invasion * No evidence of metastatic disease in either regional or distal lymph nodes, or other organs * Pre-entry CT scans of the upper abdomen and chest and Endoscopic Ultrasound (EUS) of the tumor and regional lymph nodes are required. Fusion PET scans are suggested for any indeterminate lesions * Zubrod Performance Status 0-1 * Participants must be have oral intake of greater than 1700 calories a day * Patient must not have had a second malignancy, other than curable non-melanoma skin cancer or cervical cancer in situ, unless disease free for greater than or equal to 3 years and deemed cured by their hematologist and/or oncologist * Staging procedures should be performed prior to study entry * All patients or legally authorized representative must sign a study-specific informed consent prior to randomization.
Exclusion criteria
* Prior major esophageal surgery * Patients who are unable to tolerate endoscopic procedures * Due to the possible toxic effects of photodynamic therapy and endoscopic sedation to embryos, pregnant or lactating women or men unable or unwilling to practice contraception are excluded * Patients with an uncontrolled diabetes, heart disease, or hypertension * Patient and/or legally authorized representative who are unable to comprehend the study requirements or who are not likely to comply with the study parameters.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Dysplasia on Histology at 12 Months | 12 months post therapy | All specimens were reviewed by two expert GI pathologists for presence of and/or level of dysplasia in Barrett's Esophagus |
| Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | 12 months post therapy | Whether or not positive fish markers measured by polysomy were associated with outcomes. Markers in this study include: 9q21 /017q (her2) / 8q24/ 20q / CEP17 / 17p. Polysomy and Trisomy were documented. |
| Change in Quality of Life | end of study | Quality of life in both groups (EMR and EMR with photodynamic therapy) SF36 |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from December 1, 2005 thru April 26, 2011 at Mayo Clinic in Rochester, Minnesota.
Pre-assignment details
We intended to recruit 100 patients with early cancer and were able to recruit a total of 124 patients in this single center randomized trial. A total of 73 patients could actually be randomized due to inability to completely remove the cancer, finding evidence of high risk of metastasis, or refusing randomization to photodynamic therapy.
Participants by arm
| Arm | Count |
|---|---|
| Endoscopic Mucosl Resection patients will undergo endoscopic mucosal resection at time of endoscopy if indicated | 36 |
| Photodynamic Therapy patients will have endoscopic mucosal resection (if indicated at time of endoscopy) followed by photodynamic therapy. | 37 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | completed less than 12 months return | 10 | 18 |
| Overall Study | decided to have esophagectomy | 1 | 2 |
Baseline characteristics
| Characteristic | Endoscopic Mucosl Resection | Photodynamic Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 25 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 12 Participants | 25 Participants |
| Region of Enrollment United States | 36 participants | 37 participants | 73 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 33 Participants | 31 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 36 | 21 / 37 |
| serious Total, serious adverse events | 1 / 36 | 4 / 37 |
Outcome results
Primary
Change in Quality of Life
Quality of life in both groups (EMR and EMR with photodynamic therapy) SF36
Time frame: end of study
Population: 25 patients did not return completed SF36 at 12 month of follow up their results were not used in final analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Endoscopic Mucosal Resection | Change in Quality of Life | qaulity of life remained the same of improved | 9 participants |
| Endoscopic Mucosal Resection | Change in Quality of Life | decrease in qualify of life | 1 participants |
| Photodynamic Therapy | Change in Quality of Life | qaulity of life remained the same of improved | 6 participants |
| Photodynamic Therapy | Change in Quality of Life | decrease in qualify of life | 0 participants |
p-value: 0.2Chi-squared
Primary
Fluorescence In Situ Hybridization (FISH) Markers at 12 Months.
Whether or not positive fish markers measured by polysomy were associated with outcomes. Markers in this study include: 9q21 /017q (her2) / 8q24/ 20q / CEP17 / 17p. Polysomy and Trisomy were documented.
Time frame: 12 months post therapy
Population: 4 participants in the PDT group completed at least 3 months of follow up but not 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Endoscopic Mucosal Resection | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | Decrease level of dysplasia post therapy | 7 participants |
| Endoscopic Mucosal Resection | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | no change or worsening of dysplasia post therapy | 4 participants |
| Photodynamic Therapy | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | no change or worsening of dysplasia post therapy | 5 participants |
| Photodynamic Therapy | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | Decrease level of dysplasia post therapy | 8 participants |
| Photodynamic Therapy FISH POSITIVE | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | Decrease level of dysplasia post therapy | 6 participants |
| Photodynamic Therapy FISH POSITIVE | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | no change or worsening of dysplasia post therapy | 2 participants |
| Photodynamic Therapy FISH NEGATIVE | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | Decrease level of dysplasia post therapy | 5 participants |
| Photodynamic Therapy FISH NEGATIVE | Fluorescence In Situ Hybridization (FISH) Markers at 12 Months. | no change or worsening of dysplasia post therapy | 0 participants |
p-value: 0.34Chi-squared
Primary
Level of Dysplasia on Histology at 12 Months
All specimens were reviewed by two expert GI pathologists for presence of and/or level of dysplasia in Barrett's Esophagus
Time frame: 12 months post therapy
Population: 4 participants in the photodynamic therapy group completed at least 3 but less than 12 months follow up post therapy, so they were not included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Endoscopic Mucosal Resection | Level of Dysplasia on Histology at 12 Months | Decreases in dysplasia from enrollment | 10 paricipants |
| Endoscopic Mucosal Resection | Level of Dysplasia on Histology at 12 Months | No improvement or worsened level of dysplasia | 15 paricipants |
| Photodynamic Therapy | Level of Dysplasia on Histology at 12 Months | Decreases in dysplasia from enrollment | 11 paricipants |
| Photodynamic Therapy | Level of Dysplasia on Histology at 12 Months | No improvement or worsened level of dysplasia | 2 paricipants |
p-value: 0.0098Fisher Exact