Clinical trial NCT00665197: Palliative Radiotherapy and Brachytherapy for Oesophageal Cancer Dysphagia
Official title: Improving Outcomes in Radiotherapy Using New Strategies of Treatment Delivery With Focus on Oesophageal Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophageal Cancer
Keywords: Esophageal cancer
Brachytherapy
Radiotherapy
Palliation
Dysphagia
Lead sponsor: International Atomic Energy Agency
Sponsor class: OTHER_GOV
First posted: 2008-04-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 81
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypothesis: In the management of advanced oesophageal cancer, to determine if a shorter regime of external beam radiotherapy (using higher daily doses, and combined with intraluminal high dose rate brachytherapy) is not inferior in the palliation of dysphagia than a more protracted course of external beam radiotherapy (using lower daily doses and combined with equal intraluminal high dose rate brachytherapy).

Detailed description: This is a prospective, pragmatic and multi-centre clinical trial, without blinding or masking to the randomly assigned treatment. Patient registration and randomization are centralized. There are two arms to the study, expecting an equal numbers of patients randomized to each arm. Stratification will by according to: (1) treating institution/country, and (2) baseline Stage (M1 = distant metastases versus M0 = no distant metastases). The primary statistical analysis will be conducted as an "intention-to-treat" clinical trial.

A cost-effectiveness analysis is not required because the main contrast is between 5 and 10 fractions of EBRT, where 5 fractions are less expensive than 10 fractions. This protocol follows the recommendations of CONSORT for the reporting of non-inferiority and equivalence trials. The active control is 30 Gy in 10 fractions, and the new therapy is 20 Gy in 5 fractions.

Eligibility criteria: Inclusion Criteria:

* Endoscopic and biopsy-proven carcinoma of the esophagus, either Adenocarcinoma or Squamous cell carcinoma;
* Lesions of the thoracic oesophagus and the abdominal oesophagus but not involving the cardia of the stomach. (The oesophagus extends from the cricopharyngeus muscle at the level of the cricoid cartilage to the GEJ junction. The most proximate cervical oesophagus extends approximately 2-3 cm distal to the cricopharyngeus muscle approximately 18 cm from the incisors, and is excluded from this study; however the remaining oesophagus is included in this study, including the last 1-2 cm of the oesophagus which is intra-abdominal and up to the GEJ.);
* Dysphagia immediately prior to the first HDR ILBT session (based on a 4-question summary score of 4-15 (i.e. less than a score of 16) using four of the questions from the EORTC QLQ OES-18 measure;
* Able to insert the intra-esophageal applicator (Dilatation is allowed to open up the tumor/lumen to facilitate insertion, and this does not preclude eligibility. Any oesophageal stent must be removed prior to brachytherapy because metal stents may inappropriately increase the dose of radiation to the esophageal wall by approximately 10%.\]);
* Karnofsky is between 40 and 90, inclusive and at baseline (no patient can be 100 as all will have at least dysphagia from disease at baseline; patients with KPS \<40 are not eligible for this study);
* Eligible for radiotherapy (e.g. any pacemaker is not within 2.5 cm of the outside of the field edge for the EBRT component of therapy);
* Signed informed consent.

Exclusion Criteria:

* Age less than 18;
* Patients suitable for curative treatment with either surgery or chemo-radiation;
* Tracheo-esophageal fistula, or deep mucosal ulceration;
* Perforation or massive esophageal bleeding ;
* Previous treatment (e.g. chemotherapy, radiation therapy, laser therapy or surgery) for esophageal cancer (gastrostomy or PEG does not constitute exclusion criteria, and should be considered for patients with complete obstruction or where there has been substantial loss in body weight prior to diagnosis);
* Stents in situ (i.e. not removed prior to the first HDR ILBT);
* Previous thoracic radiation therapy for any cause, either EBRT or ILBT;
* Evidence of other uncontrolled malignancies, or evidence of synchronous head and neck or lung primary cancers (regardless of whether those malignancies could be managed with curative intent);
* Failure to complete all baseline assessments required for the study, including patient-elicited scores for symptoms and QOL;
* Pregnant or lactating patients.

Primary outcomes:
measure: Dysphagia relief
timeFrame: 3 years
Secondary outcomes:
measure: Quality of life
timeFrame: 3 years
measure: Treatment Toxicity
timeFrame: 3 years
Other outcomes:
Locations:
city: Credit Valley
country: Canada
facility: Credit Valley Hospital Statistical Centre
state: Ontario
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences
state: Beijing
city: Zagreb
country: Croatia
facility: University of Zagreb Clinical Hospital
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Parel
city: Lahore
country: Pakistan
facility: Institute of Nuclear Medicine and Oncology
state: Punjab
city: Johannesburg
country: South Africa
facility: University of the Witwatersrand Department of Radiat. Oncology
state: Parktown
city: Bangkok
country: Thailand
facility: Mahidol University Faculty of Medicine Siriraj Hospital
state: Siriraj
Study officials:
affiliation: International Atomic Energy Agency
name: Eduardo Rosenblatt, MD
role: STUDY_CHAIR
References:
citation: Sur RK, Donde B, Levin VC, Mannell A. Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer. Int J Radiat Oncol Biol Phys. 1998 Jan 15;40(2):447-53. doi: 10.1016/s0360-3016(97)00710-4.
citation: Sur RK, Levin CV, Donde B, Sharma V, Miszczyk L, Nag S. Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study. Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):127-33. doi: 10.1016/s0360-3016(02)02702-5.
citation: Gaspar LE, Nag S, Herskovic A, Mantravadi R, Speiser B. American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA. Int J Radiat Oncol Biol Phys. 1997 Apr 1;38(1):127-32. doi: 10.1016/s0360-3016(97)00231-9.
citation: Kumar MU, Swamy K, Supe SS, Anantha N. Influence of intraluminal brachytherapy dose on complications in the treatment of esophageal cancer. Int J Radiat Oncol Biol Phys. 1993 Dec 1;27(5):1069-72. doi: 10.1016/0360-3016(93)90525-z.