Dose Escalated Adaptive RadioTherapy in Definitive Chemo-radiotherapy for Esophageal Cancer

NCT04086901 | Terminated

• 1 other identifier: DART
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief Summary

In Denmark, 1000 new cases of esophageal and gastro-esophageal junction cancer occur every year. Surgery is the primary treatment for patients with localized disease who are considered medically and technically operable. For patients deemed non-resectable, definitive chemoradiotherapy is the treatment of choice, but despite treatment with curative intent, these patients have a poor prognosis, with a median survival of less than 20 months and a 5-year survival at 15-25% in clinical studies This study will examine the effect of escalation of increasing the radiation dose to the most Positron Emissions Tomografi (PET) avid part of the tumour and lymph nodes compared to a standard uniform dose distribution.

Conditions

Esophageal Cancer

Keywords

Radiotherapy; Dose escalation; Definitive chemo-radiotherapy

Outcome Measures

Primary Outcomes (1)

• Loco-regional control

  Loco-regional control evaluated with Flour-Deoxy-Glucose /Positron Emissions Tomografi (FDG-PET)

  12 months

Secondary Outcomes (17)

• Acute and late toxicity

  5 years

• Overall survival

  1 and 5 years

• Progression-free survival

  1 and 5 years

• Hospitalization

  12 months

• Mean and maximum dose distributions

  6 months

Study Arms (2)

Dose escalation Arm

EXPERIMENTAL

Chemo-radiotherapy with radiotherapy dose escalation based on Flour-Deoxy-Glucose /Positron Emissions Tomografi (FDG/PET) scans

Radiation: Radiotherapy dose escalation

Standard

NO INTERVENTION

Standard chemo-radiotherapy

Interventions

Radiotherapy dose escalation RADIATION

Flour-Deoxy-Glucose /Positron Emissions Tomografi (FDG-PET) scans will be used to identify and delineate the tumour sub-volumes with the highest tracer uptake to guide the dose-escalation. The dose to the Gross tumor volume (GTV) will be escalated to a high dose while clinical target volume (CTV) and planning target volume (PTV) will be treated with standard dose.

Dose escalation Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically verified squamous cell or adenocarcinoma (including signet cell carcinoma) of the oesophagus or GEJ.
• Multi-Disciplinary Team (MDT) assessment and treatment recommendation; deemed nonresectable and/or inoperable.
• TNM stage (8th edition): cT1-4a or cN+, cM0-1 (M1 disease limited to metastatic lymph nodes)
• Age ≥18 years.
• Performance status ≤2.
• Adequate cardiac, lung and renal function measured according to local guidelines.
• Adequate laboratory findings:
• haematological: haemoglobin \> 90 g/L, absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 75 x 109/L
• hepatic: bilirubin ≤ 1.5 x ULN, ALAT ≤ 3 x ULN
• renal: creatinine ≤ 1.5 x ULN
• Suitability to undergo curatively intended chemoradiation therapy.
• Ability to adhere to procedures for study and follow-up.
• Women must present a negative pregnancy test. Fertile men and women must use effective contraception. Fertile women included in the study must use oral contraceptives, intrauterine devices, depot injection of progestin subdermal implantation, a hormonal vaginal ring, or transdermal patch during the study treatment and one month after.
• Signed informed consent to participate in the study, including acceptance that dose plan and scans will be stored in a national dose plan bank, and the remaining data stored in a central database.
• A standard plan for radiotherapy with homogenous 50 Gy / 25 fractions, meeting all dose constraints for normal tissue, must be achievable.

You may not qualify if:

• Prior oncological treatment or surgical resection for the present disease
• Broncho-pulmonary fistula verified by bronchoscopy
• Any other active malignancies which may compromise study protocol or endpoints except for basal or squamous cell skin cancer
• Any unstable systemic disease (including clinically significant cardiovascular disease, unstable angina, New York Heart Association (NYHA) grade III-IV congestive heart, severe hepatic, renal or metabolic disease or active inflammatory bowel disease)
• Symptomatic peripheral neuropathy greater than grade 1 (CTCAE version 4.03)
• Any other serious or uncontrolled illness which in the opinion of the investigator makes it undesirable for the patient to enter the trial
• Severely decreased lung function

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital Skejby: collaborator
• Rigshospitalet, Denmark: collaborator
• Odense University Hospital: collaborator

Study Sites (3)

Rigshospitalet

Copenhagen, Capital Region, 2100, Denmark

Location

Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

Location

Odense Universityhospital

Odense, Fyn, 5000, Denmark

Location

Related Publications (1)

• Sakanaka K, Ishida Y, Fujii K, Ishihara Y, Nakamura M, Hiraoka M, Mizowaki T. Radiation Dose-escalated Chemoradiotherapy Using Simultaneous Integrated Boost Intensity-Modulated Radiotherapy for Locally Advanced Unresectable Thoracic Oesophageal Squamous Cell Carcinoma: A Single-institution Phase I Study. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):191-201. doi: 10.1016/j.clon.2020.07.012. Epub 2020 Aug 4.

  PMID: 32768158 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Hanna R Mortensen, MD PhD

  Aarhus University Hospital and Aarhus University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized trial

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: September 12, 2019
• Study Start: January 1, 2020
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: March 9, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (3)