Hypofractionated Definitive Chemoradiotherapy for Oesophageal Cancer

NCT07632079 | Recruiting Phase 2 DMC

• 1 other identifier: NL-010499
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Locally Advanced Esophageal or GE Junction Cancer

Keywords

Definitive chemoradiotherapy; Hypofractionation; Locally advanced esophageal or GE junction cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who complete all 20 fractions of radiotherapy and receive all 6 cycles of concurrent chemotherapy.

  Feasibility, defined as ≥50% of patients completing all 20 radiotherapy fractions and all 6 planned chemotherapy cycles.

  Immediately after the treatment.

Secondary Outcomes (3)

• Incidence and severity of grade ≥4 RIL, and absolute lymphocyte count nadirs.

  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.

• Incidence of grade ≥3 acute toxicity.

  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.

• Proportion of patients who complete at least 19 of 20 radiotherapy fractions and at least 5 out of 6 planned chemotherapy cycles.

  Immediately after the treatment.

Other Outcomes (6)

• Incidence and severity of treatment-related adverse events.

  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

• Progression Free Survival (PFS) and Overall Survival (OS).

  1 year, 2 years, 3 years, 4 years, 5 years

• Patient-reported quality of life during and after the treatment.

  Baseline, 3 months after treatment, 1 year, 2 years, 3 years, 4 years, 5 years

Study Arms (1)

Hypofractionated definitive chemoradiotherapy

EXPERIMENTAL

Participants receive 20 fractions of 2.4 Gy with concurrent 6 cycles of carboplatin and paclitaxel in 4 weeks.

Radiation: Hypofractionation; Drug: carboplatin + paclitaxel (CP)

Interventions

Hypofractionation RADIATION

20 fractions of 2.4 Gy

Hypofractionated definitive chemoradiotherapy

carboplatin + paclitaxel (CP) DRUG

6 cycles of carboplatin (AUC 2) and paclitaxel (50 mg/m2) given every 4-5 days, 6 cycles in total in 4 weeks.

Hypofractionated definitive chemoradiotherapy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• University Medical Center Groningen: collaborator

Study Sites (7)

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

Gelre Ziekenhuizen

Apeldoorn, Netherlands

NOT YET RECRUITING

Radiotherapiegroep

Apeldoorn, Netherlands

NOT YET RECRUITING

UMCG

Groningen, Netherlands

RECRUITING

Zuyderland Medisch Centrum

Heerlen, Netherlands

NOT YET RECRUITING

Maastro

Maastricht, Netherlands

NOT YET RECRUITING

Radboud UMC

Nijmegen, Netherlands

NOT YET RECRUITING

MeSH Terms

Interventions

Radiation Dose Hypofractionation; CP protocol

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Peter S.N. van Rossum

  Amsterdam University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iris Agterberg

CONTACT

+31 204441571; i.agterberg@amsterdamumc.nl

Dr. P.S.N. van Rossum

CONTACT

p.s.n.vanrossum@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: June 8, 2026
• Study Start: April 28, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (7)