hypofractionation
Radiation20 fractions of 2.4 Gy
Recruiting
NCT Number: NCT07632079
Hypofractionated Definitive Chemoradiotherapy for Oesophageal Cancer
The goal of this clinical trial is to learn if hypofractionation of definitive chemoradiotherapy can treat patients with locally advanced esophageal cancer. The main question it aims to answer is if this treatment is feasible and safe. We also want to investigate the toxicity, in particular the radiation-induced lymphopenia.
Normally, definitive chemoradiotherapy for patients with locally advanced esophageal cancer consist of 28 fractions of 1.8 Gy with concurrent 6 cycles of carboplatin and paclitaxel in 5.5 weeks. In this study, participants will receive 20 fractions of 2.4 Gy with concurrent 6 cycles of carboplatin and paclitaxel in 4 weeks. The follow-up will be conform standard-of-care.
Recruiting
Interested in participating?
Request InfoKey information
Age range
18 year and older
Sex eligibility
All sexes
Study type
Interventional
Phase
Phase 2
Primary location
Amsterdam UMC, Amsterdam, Netherlands
Loading trial locations.
Who can participate
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
- Age ≥18 years.
- Histologically confirmed oesophageal or GOJ carcinoma (adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large cell carcinoma or undifferentiated carcinoma).
- An oesophageal tumour location can involve the proximal, middle and/or distal third of the oesophagus.
- If the tumour extends below the GOJ into the cardia, the bulk of the tumour must involve the oesophagus or GOJ (i.e. Siewert type I or II). The tumour should not extend more than 5 cm into the stomach.
- Clinical stage cT1N1-3M0 or cT2-4aN0-3M0, using the Tumour-Node-Metastasis classification system (TNM, 8th edition), deemed suitable for definitive CRT with curative intent.
- No evidence of distant metastases (M0), as confirmed by standard staging procedures including Fluorine-18 Fluorodeoxyglucose (18F-FDG) PET/CT.
- World Health Organization (WHO) performance status 0-2.
- Adequate hematologic, renal, and hepatic function:
- Platelet count ≥100 × 10⁹/L
- Absolute neutrophil count ≥1.5 × 10⁹/L
- Glomerular filtration rate ≥50 mL/min
- Total bilirubin ≤1.5 × upper normal limit
- Written informed consent obtained before any study-specific procedures.
- Able to comply with study procedures and scheduled follow-up.
Exclusion criteria
- High grade dysplasia without histological evidence of invasive carcinoma.
- Presence of distant metastases (M1).
- Patients with pathological lymph nodes at both supraclavicular and celiac trunk level.
- Prior thoracic or upper abdominal radiotherapy that would preclude safe delivery of the planned radiotherapy dose.
- Prior chemotherapy for oesophageal or gastric cancer.
- Presence of an oesophageal stent.
- Active uncontrolled infection.
- Clinically significant comorbidities that would preclude safe administration of CRT (e.g. severe pulmonary, cardiac, or hepatic impairment).
- Pregnancy or breastfeeding.
- Known hypersensitivity to paclitaxel, carboplatin, or any of their excipients.
- History of malignancies, with the exception of basal cell carcinoma of the skin, ductal carcinoma in situ of breast, cervical intraepithelial neoplasia of uterine cervix, or other malignancies that do not interfere with the prognosis of oesophageal cancer.
Treatment and study plan
carboplatin + paclitaxel (CP)
Drug6 cycles of carboplatin (AUC 2) and paclitaxel (50 mg/m2) given every 4-5 days, 6 cycles in total in 4 weeks.
Primary outcomes
-
Proportion of patients who complete all 20 fractions of radiotherapy and receive all 6 cycles of concurrent chemotherapy.
Time frame: Immediately after the treatment.
Feasibility, defined as ≥50% of patients completing all 20 radiotherapy fractions and all 6 planned chemotherapy cycles.
Secondary outcomes
-
Incidence and severity of grade ≥4 RIL, and absolute lymphocyte count nadirs.
Time frame: Baseline, after first week of treatment, after second week of treatment, after third week of treatment, after fourth week of treatment, 3 months after the treatment.
The RIL will be scored according to CTCAE v5.0.
-
Incidence of grade ≥3 acute toxicity.
Time frame: Baseline, after first week of treatment, after second week of treatment, after third week of treatment, after fourth week of treatment, 3 months after the treatment.
The acute toxicity will be scored according to CTCAE v5.0.
-
Proportion of patients who complete at least 19 of 20 radiotherapy fractions and at least 5 out of 6 planned chemotherapy cycles.
Time frame: Immediately after the treatment.
Other outcomes
-
Incidence and severity of treatment-related adverse events.
Time frame: After first week of treatment, after second week of treatment, after third week of treatment, after fourth week of treatment, 3 months after treatment, 1 year, 2 years, 3 years, 4 years, 5 years
The adverse events will be scored according to CTCAE v5.0.
-
Progression Free Survival (PFS) and Overall Survival (OS).
Time frame: 1 year, 2 years, 3 years, 4 years, 5 years
-
Patient-reported quality of life during and after the treatment.
Time frame: Baseline, 3 months after treatment, 1 year, 2 years, 3 years, 4 years, 5 years
Assessed using validated questionnaires collected through the POCOP national prospective cohort.
-
Costs associated with the treatment.
Time frame: 3 months after treatment.
-
Feasibility and clinical outcomes of the treatment compared to a propensity score-matched standard-of-care cohort.
Time frame: 3 months after treatment, 1 year, 2 years, 3 years, 4 years, 5 years
A propensity score-matched cohort will be assembled using data from the University Medical Center Groningen (UMCG) prospective registry for toxicity comparison, and the Netherlands Cancer Registry (NCR) for OS comparison.
-
1. Association of dosimetric parameters of the lungs and heart with radiation-induced lymphopenia. 2. Association of target volume size with radiation-induced lymphopenia.
Time frame: 1 month after treatment
- Associations between predefined lung and heart dose-volume parameters and radiation-induced lymphopenia will be assessed. Dose-volume parameters will include V5Gy, V10Gy, V15Gy, V20Gy, V25Gy, V30Gy, V35Gy, V40Gy, V45Gy, and mean dose. Radiation-induced lymphopenia will be assessed as grade ≥3 at any time during treatment, grade ≥4 at any time during treatment, and grade ≥3 in week 3 of treatment. Associations will be reported separately for each parameter and definition as odds ratios with 95% confidence intervals.
- Associations between the predefined target volume parameter 'planning target volume' (PTV) measured in cubic centimeters, and radiation-induced lymphopenia will be assessed using the same definitions as described above. Associations will be reported separately for PTV and radiation-induced lymphopenia definition as odds ratio (per 100 cm3) with 95% confidence interval.
Study contacts
Contact information is provided by the study sponsor or research team.
Dr. P.S.N. van Rossum
CONTACT
Iris Agterberg
CONTACT
Sponsors and collaborators
Lead sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Other
Collaborators
- University Medical Center Groningen
Registry information
Official study title
HYpofractionated Definitive chemoRadiotherapy for Oesophageal Cancer (HYROC): a Multicenter Phase II Feasibility Study
Acronym: HYROC
Important dates
- Study start
- 2026
- Primary completion
- 2028
- Study completion
- 2028
- First posted
- Jun 8, 2026
- Registry last updated
- Jun 8, 2026
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.