Establishing Best Treatment Strategy for T4 Esophageal Cancer

Official title

A Pilot Study to Establish Best Treatment Strategy for T4 Esophageal Cancer

Overview

The goal of this clinical trial is to investigate the safety and efficacy of a new treatment approach for T4-stage esophageal cancer, which involves chemoradiotherapy after induction chemotherapy. The main questions it aims to answer are: * Does the new induction chemotherapy followed by chemoradiation reduce esophageal perforation rate? * Does the new induction chemotherapy followed by chemoradiation increase treatment response rate and patient survival? Researchers will analyze the above data to see if the new treatment approach works to treat T4 esophageal cancer. Participants will: * Receive induction chemotherapy for 4 to 8 cycles, followed by chemoradiation therapy if downstage to T3 * Visit the clinic once every week for checkups and tests * Keep a diary of their symptoms

Detailed description

The treatment of T4-stage esophageal cancer is challenging because of a high esophageal perforation rate (19%) after concurrent chemoradiotherapy. This research aims to investigate whether a novel sequential chemoradiotherapy approach can improve the treatment response rate and reduce the incidence of esophageal perforation in participants with T4-stage esophageal cancer. The proposed novel treatment strategy involves induction chemotherapy for 4 to 8 cycles. It is followed by concurrent chemoradiotherapy if down-stage had been achieved by induction chemotherapy. The study will be conducted in two phases, starting with a phase I study to determine safety, followed by a phase II study to evaluate overall efficacy. Expected outcomes include improved treatment response rates and reduced esophageal perforation rates in T4-stage esophageal cancer, offering a better treatment option for these patients.

Interventions

• Combination product "Docetaxel", "Cisplatin", "fluorouracil", "Radiation"
  Induction chemotherapy with Docetaxel, Cisplatin, and fluorouracil for 4 to 8 cycles, followed by concurrent chemoradiotherapy with Cisplatin and Radiation 30.6-40 Gy.

Primary outcome measures

• Overall response rate of the treatment [Time frame: At week 8, week 16, and 4 weeks after completion of concurrent chemoradiotherapy (CCRT).]
• Duration of response (DOR) [Time frame: At week 8, week 16, and 4 weeks after completion of CCRT. Thereafter, every 3 months.]

Secondary outcome measures (4)

• Esophageal perforation rate [Time frame: At week 8, week 16, and 4 weeks after completion of CCRT. And at anytime when participants suffer from symptoms in suspicious of esophageal perforation, eg. chest pain, hemoptysis, and fever.]
• Adverse events of treatment [Time frame: During treatment (up to 24 weeks)]
• Progression-free survival [Time frame: At week 8, week 16, and 4 weeks after completion of CCRT. Thereafter, every 3 months.]
• Overall survival time [Time frame: At week 8, week 16, and 4 weeks after completion of CCRT. Thereafter, every 3 months.]

Eligibility criteria

Inclusion criteria

• Histologically confirmed esophageal squamous cell carcinoma
• Tumor or lymph nodes invade adjacent organs (T4 stage)
• Aged between 18-70 years old
• Patient health status score Eastern Cooperative Oncology Group (ECOG) performance status (PS) <2
• Hemoglobin ≥ 10 g/L, absolute neutrophil count ≥ 2×10\^3/L, platelet count ≥ 100×10\^9/L, total bilirubin ≤ 1.5 mg/L, serum transaminases ≤ 105 U/L, creatinine clearance ≥ 40 mL/min.

Exclusion criteria

• Previous chemotherapy history
• Myocardial infarction within the last three months
• History of unstable angina, interstitial pneumonia, fibrotic lung disease, or severe emphysema
• Has other malignancies currently
• Uncontrolled infection
• Pregnancy or lactation
• Perforated esophagus at the time of diagnosis

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Cheng Kung University Hospital — Tainan

Publications

• Chan WL, Choi CW, Wong IY, Tsang TH, Lam AT, Tse RP, Chan KK, Wong C, Law BT, Cheung EE, Chan SY, Lam KO, Kwong D, Law S. Docetaxel, Cisplatin, and 5-FU Triplet Therapy as Conversion Therapy for Locoregionally Advanced Unresectable Esophageal Squamous Cell Carcinoma. Ann Surg Oncol. 2023 Feb;30(2):861-870. doi: 10.1245/s10434-022-12694-8. Epub 2022 Oct 28. PMID 36307666
• Satake H, Tahara M, Mochizuki S, Kato K, Hara H, Yokota T, Kiyota N, Kii T, Chin K, Zenda S, Kojima T, Bando H, Yamazaki T, Iwasa S, Honma Y, Hamauchi S, Tsushima T, Ohtsu A. A prospective, multicenter phase I/II study of induction chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) followed by chemoradiotherapy in patients with unresectable locally advanced esophageal carcinoma. Cancer PMID 27193097
• Makino T, Yamasaki M, Miyazaki Y, Wada N, Takahashi T, Kurokawa Y, Nakajima K, Takiguchi S, Mori M, Doki Y. Utility of initial induction chemotherapy with 5-fluorouracil, cisplatin, and docetaxel (DCF) for T4 esophageal cancer: a propensity score-matched analysis. Dis Esophagus. 2018 Apr 1;31(4). doi: 10.1093/dote/dox130. PMID 29190316

Identifiers

NCT: NCT06531434 · A-BR-113-045

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗