Clinical trial NCT06531434: Establishing Best Treatment Strategy for T4 Esophageal Cancer
Official title: A Pilot Study to Establish Best Treatment Strategy for T4 Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer TNM Staging Primary Tumor (T) T4
Keywords: T4 esophageal cancer
Induction chemotherapy
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
First posted: 2024-08-01
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will receive an induction chemotherapy regimen consisting of 4-8 cycles of docetaxel, cisplatin, and fluorouracil. It is followed by concurrent chemoradiotherapy if down-stage had been achieved by induction chemotherapy.
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed esophageal squamous cell carcinoma
2. Tumor or lymph nodes invade adjacent organs (T4 stage)
3. Aged between 18-70 years old
4. Patient health status score Eastern Cooperative Oncology Group (ECOG) performance status (PS) \<2
5. 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:

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

Primary outcomes:
measure: Overall response rate of the treatment
timeFrame: At week 8, week 16, and 4 weeks after completion of concurrent chemoradiotherapy (CCRT).
measure: Duration of response (DOR)
timeFrame: At week 8, week 16, and 4 weeks after completion of CCRT. Thereafter, every 3 months.
Secondary outcomes:
measure: Esophageal perforation rate
timeFrame: 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.
measure: Adverse events of treatment
timeFrame: During treatment (up to 24 weeks)
measure: Progression-free survival
timeFrame: At week 8, week 16, and 4 weeks after completion of CCRT. Thereafter, every 3 months.
measure: Overall survival time
timeFrame: At week 8, week 16, and 4 weeks after completion of CCRT. Thereafter, every 3 months.
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
References:
citation: 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.
citation: 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 Chemother Pharmacol. 2016 Jul;78(1):91-9. doi: 10.1007/s00280-016-3062-2. Epub 2016 May 18.
citation: 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.