Endoscopic Therapy of Early Cancer in Barretts Esophagus

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT00217087
Collaborator
National Cancer Institute (NCI) (NIH)
73
1
2
81
0.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Endoscopic Mucosal Resection
  • Procedure: Photodynamic Therapy
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
73 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Endoscopic Therapy of Early Cancer in Barretts Esophagus
Study Start Date :
Sep 1, 2005
Actual Primary Completion Date :
Jun 1, 2012
Actual Study Completion Date :
Jun 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Other: Endoscopic Mucosal Resection

Patients will undergo endoscopic mucosal resection at time of endoscopy if indicated.

Procedure: Endoscopic Mucosal Resection
Endoscopic mucosal resection at time of endoscopy if indicated.

Other: Photodynamic Therapy

Patients will have endoscopic mucosal resection with photodynamic therapy.

Procedure: Endoscopic Mucosal Resection
Endoscopic mucosal resection at time of endoscopy if indicated.

Procedure: Photodynamic Therapy
Porfimer sodium 2mg/kg
Other Names:
  • Photofrin
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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.

    3. Change in Quality of Life [end of study]

      Quality of life in both groups (EMR and EMR with photodynamic therapy) SF36

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Kenneth K. Wang, M.D., Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kenneth K. Wang, Professor of Medicine, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT00217087
    Other Study ID Numbers:
    • 1399-05
    • R01CA111603
    First Posted:
    Sep 22, 2005
    Last Update Posted:
    Dec 24, 2015
    Last Verified:
    Nov 1, 2015
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Patients were recruited from December 1, 2005 thru April 26, 2011 at Mayo Clinic in Rochester, Minnesota.
    Pre-assignment Detail 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.
    Arm/Group Title Endoscopic Mucosal Resection Photodynamic Therapy
    Arm/Group Description Patients will undergo endoscopic mucosal resection at time of endoscopy if indicated. Patients will have endoscopic mucosal resection (if indicated at time of endoscopy) followed by photodynamic therapy.
    Period Title: Overall Study
    STARTED 36 37
    COMPLETED 25 17
    NOT COMPLETED 11 20

    Baseline Characteristics

    Arm/Group Title Endoscopic Mucosl Resection Photodynamic Therapy Total
    Arm/Group Description patients will undergo endoscopic mucosal resection at time of endoscopy if indicated patients will have endoscopic mucosal resection (if indicated at time of endoscopy) followed by photodynamic therapy. Total of all reporting groups
    Overall Participants 36 37 73
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    13
    36.1%
    12
    32.4%
    25
    34.2%
    >=65 years
    23
    63.9%
    25
    67.6%
    48
    65.8%
    Sex: Female, Male (Count of Participants)
    Female
    3
    8.3%
    6
    16.2%
    9
    12.3%
    Male
    33
    91.7%
    31
    83.8%
    64
    87.7%
    Region of Enrollment (participants) [Number]
    United States
    36
    100%
    37
    100%
    73
    100%

    Outcome Measures

    1. Primary Outcome
    Title Level of Dysplasia on Histology at 12 Months
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title Endoscopic Mucosal Resection Photodynamic Therapy
    Arm/Group Description Patients will undergo endoscopic mucosal resection at time of endoscopy if indicated. Patients will have endoscopic mucosal resection (if indicated at time of endoscopy) followed by photodynamic therapy.
    Measure Participants 25 13
    Decreases in dysplasia from enrollment
    10
    11
    No improvement or worsened level of dysplasia
    15
    2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Endoscopic Mucosal Resection, Photodynamic Therapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0098
    Comments
    Method Fisher Exact
    Comments
    2. Primary Outcome
    Title Fluorescence In Situ Hybridization (FISH) Markers at 12 Months.
    Description 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

    Outcome Measure Data

    Analysis Population Description
    4 participants in the PDT group completed at least 3 months of follow up but not 12 months
    Arm/Group Title Endoscopic Mucosal Resection FISH Polysomy Negative Endoscopic Mucosal Resection FISH Positive Positive Photodynamic Therapy FISH POSITIVE Photodynamic Therapy FISH NEGATIVE
    Arm/Group Description FISH cytology results prior to therapy were negative FISH cytology results were positive prior to therapy FISH cytology results were positive prior to therapy FISH cytology results prior to therapy were negative
    Measure Participants 11 13 8 5
    Decrease level of dysplasia post therapy
    7
    19.4%
    8
    21.6%
    6
    8.2%
    5
    NaN
    no change or worsening of dysplasia post therapy
    4
    11.1%
    5
    13.5%
    2
    2.7%
    0
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Endoscopic Mucosal Resection, Photodynamic Therapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.34
    Comments
    Method Chi-squared
    Comments
    3. Primary Outcome
    Title Change in Quality of Life
    Description Quality of life in both groups (EMR and EMR with photodynamic therapy) SF36
    Time Frame end of study

    Outcome Measure Data

    Analysis Population Description
    25 patients did not return completed SF36 at 12 month of follow up their results were not used in final analysis.
    Arm/Group Title Endoscopic Mucosal Resection Endoscopic Mucosal Resection and Photodynamic Therapy
    Arm/Group Description Patients will undergo EMR at time of endoscopy if indicated. Patients will have EMR (if indicated at time of endoscopy) followed by photodynamic therapy
    Measure Participants 10 6
    qaulity of life remained the same of improved
    9
    25%
    6
    16.2%
    decrease in qualify of life
    1
    2.8%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Endoscopic Mucosal Resection, Photodynamic Therapy
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.2
    Comments
    Method Chi-squared
    Comments the only participant who reported a decrease quality of life related that to a recent surgery not their esophagus.

    Adverse Events

    Time Frame 6 years, 2 months
    Adverse Event Reporting Description
    Arm/Group Title Endoscopic Mucosl Resection Photodynamic Therapy
    Arm/Group Description patients will undergo endoscopic mucosal resection at time of endoscopy if indicated patients will have endoscopic mucosal resection (if indicated at time of endoscopy) followed by photodynamic therapy.
    All Cause Mortality
    Endoscopic Mucosl Resection Photodynamic Therapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Endoscopic Mucosl Resection Photodynamic Therapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/36 (2.8%) 4/37 (10.8%)
    Cardiac disorders
    heart attack resulting in death 1/36 (2.8%) 1 2/37 (5.4%) 2
    Renal and urinary disorders
    Renal failure - Sepsis 0/36 (0%) 0 1/37 (2.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Respitory Failure / Sepsis 0/36 (0%) 0 1/37 (2.7%) 1
    Other (Not Including Serious) Adverse Events
    Endoscopic Mucosl Resection Photodynamic Therapy
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/36 (8.3%) 21/37 (56.8%)
    Cardiac disorders
    Atrial fibrilation 1/36 (2.8%) 1 0/37 (0%) 0
    Gastrointestinal disorders
    Bleeding 1/36 (2.8%) 1 1/37 (2.7%) 1
    Pain 0/0 (NaN) 0 1/37 (2.7%) 1
    Dysphagia 0/36 (0%) 0 6/37 (16.2%) 6
    General disorders
    Dehydration 1/36 (2.8%) 1 1/37 (2.7%) 1
    Skin and subcutaneous tissue disorders
    Photosensitivity 0/36 (0%) 0 12/37 (32.4%) 12

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Kenneth Wang MD
    Organization Mayo Clinic
    Phone 507-255-7495
    Email wang.kenneth@mayo.edu
    Responsible Party:
    Kenneth K. Wang, Professor of Medicine, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT00217087
    Other Study ID Numbers:
    • 1399-05
    • R01CA111603
    First Posted:
    Sep 22, 2005
    Last Update Posted:
    Dec 24, 2015
    Last Verified:
    Nov 1, 2015