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)
• Enrollment: 73
• Location: 1
• Arms: 2
• Duration (Months): 81
• Patients Per Site Per Month: 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
Early Stage Esophageal Adenocarcinoma; Barrett Esophagus	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: Barrett Esophagus; Dihematoporphyrin Ether

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
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.