Clinical trial NCT02606396: Cryotherapy for Malignant Dysphagia in Patients With Advanced Esophageal Cancer
Official title: Palliation of Malignant Dysphagia With Spray Cryotherapy in Patients With Advanced Esophageal Cancer: A Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Esophageal Adenocarcinoma
Lead sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Sponsor class: FED
First posted: 2015-11-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Esophageal adenocarcinoma (EAC) is one of the few cancers with a rising incidence in the United States, with an estimated 17,000 new cases diagnosed in 2012. Most patients with esophageal cancer present with tumors which are not amenable to surgery and are treated with chemotherapy and radiation. The most common and bothersome symptoms from esophageal cancer is dysphagia (difficulty swallowing). Chemotherapy and radiation are effective in shrinking tumors and allowing patients with EAC to swallow more easily; however it usually takes 1-2 months for swallowing to improve with this treatment.

Another method of shrinking esophageal tumors and allowing for better swallowing is endoscopic spray cryotherapy (freezing the tumor from inside the esophagus with the aid of an endoscope); cryotherapy is a well established method for treating cancerous and pre-cancerous esophageal disease. This is a particularly attractive treatment option, as patients with esophageal cancer usually undergo endoscopy on several occasions before starting treatment in order to biopsy and evaluate the tumor.

The goal of this study is to evaluate the effectiveness of cryotherapy in treating EAC related dysphagia in patients who are getting ready to start chemotherapy and radiation.

In order to do this the investigators are planning to invite patients who are already undergoing endoscopy for pre-chemotherapy evaluation of known EAC. Patients would undergo cryotherapy after the diagnostic portion of the endoscopy has been completed. After the cryotherapy patients will be contacted by phone in order to evaluate change in symptoms, 2 and 4 weeks after cryotherapy.

Detailed description: Endoscopic spray cryotherapy (EC) is a novel modality for destruction of tissue in the gastrointestinal tract. EC involves the endoscopic application of cryogen \[liquid nitrogen (LN)\], which destroys tissue by rapid freezing and slow thawing. Immediate effects from tissue freezing include failure of cellular metabolism, membrane damage and local ischemia. Delayed effects may include apoptosis of cancer cells and immune mediated tumor destruction. EC has been used for the treatment of mucosal EAC and palliation of malignant dysphagia since 2007 in multiple tertiary centers, including Washington University in St Louis, with positive results. EC is an attractive modality for the palliation of malignant dysphagia in EAC due to the fact that newly diagnosed patients undergo upper endoscopy (EGD) and endoscopic ultrasound (EUS) as part of initial staging; thus EC could be delivered at the time of the staging endoscopy, without burdening the patient with an additional procedure. However, prospective studies on the efficacy of EC in the short term palliation of malignant dysphagia in EAC have not been performed.

Thus, the goal of this pilot study is to evaluate the effectiveness of EC in the short term palliation of malignant dysphagia in patients with unresectable EAC.

Eligibility criteria: Inclusion Criteria:

* Patients \>18 years of age with malignant dysphagia due to locally advanced EAC (≥T3 and/or N1) who are undergoing upper endoscopic ultrasound or upper endoscopy for pre-treatment staging or symptom evaluation

Exclusion Criteria:

* Prior esophageal or gastro-esophageal junction surgery.
* Prior diagnosis of oropharyngeal dysphagia.
* Prior diagnosis of esophageal achalasia.
* Esophageal strictures unrelated to EAC
* Distant metastasis
* Dysphagia only to solid or semi-solid foods
* Need for esophageal dilation in order to pass the diagnostic upper endoscope distal to the tumor.
* Coagulopathy (INR\>2, platelets \< 50,000)
* Inability to provide informed consent.
* Marfan's syndrome

Primary outcomes:
measure: Change in dysphagia severity according to validated symptom score
timeFrame: 2 weeks after cryoablation session
Secondary outcomes:
measure: Ability to maintain oral intake evaluated by a member of the study team utilizing dysphagia assessment and oral intake assessment instruments who will contact each patient at 1-month intervals while the patient receives chemoradiation
timeFrame: Up to 12 weeks
measure: Assessment of pathologic complete response and clinical complete response at the completion of neo-adjuvant chemoradiation number one.
timeFrame: Up to 24 weeks
measure: Assessment of pathologic complete response and clinical complete response at the completion of neo-adjuvant chemoradiation number two.
timeFrame: Up to 24 weeks
measure: Incidence of procedure related adverse events, classified according to the American Society of Gastrointestinal Endoscopy lexicon
timeFrame: 1 week after each procedure; 2 to 3 weeks after each procedure and 8 weeks after completion of the last cryoablation session
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Center for Advanced Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Vladimir M Kushnir, MD
role: PRINCIPAL_INVESTIGATOR
References: