Concurrent Chemoradiotherapy After Endoscopic Resection for Stage I Esophageal Carcinoma

NCT ID: NCT04275986

Last Updated: 2021-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-20
• Study Completion Date: 2024-03-31

Brief Summary

This is a prospective single-arm study of endoscopic resection (ER) following concurrent chemoradiotherapy for stage I esophageal squamous cell carcinoma, to find if the treatment combination is useful by assessing its safety and efficacy.

Detailed Description

The objectives are to evaluate the efficacy and safety of concurrent chemoradiotherapy after endoscopic resection in early stage esophageal squamous cell carcinoma by evaluating the effectiveness, including 3-year OS, DFS, LRFS, DMFS, LCR, DMR and QOF, and analyzing the toxicity and side effects in 3 years follow-up time.

The study preliminarily explored the recurrence patterns of solely ER for early esophageal squamous cell carcinoma with high risk factors, analyzed the rationality of target areas and dose choices in the treatment regimen of concurrent chemoradiotherapy after ER, and proposed modification schemes of the target area and dose of radiotherapy. Prospectively acquired hematological samples and tissue samples during the treatment will be tested for genetic testing, single-cell genome sequencing, transcriptome and epigenomic analysis, to screen the population with high risk of recurrence or the population who will benefit from this treatment combination.

In terms of sample size, The estimates of survival rate at 3 years for operation group is 85.1% (95% CI: 82.0%, 87.7%) based on SEER study. Assuming that the survival rate at 3 years for ER+CRT is about 90.7%. The difference between operation and ER+CRT is marginal and clinically meaningless. In our study, we will target to establish that the ER+CRT is non-inferiority to operation in term of survival rate at 3 years, and further investigate the benefit of ER+CRT in safety profile and quality of life. A non-inferiority margin 10% is applied with respect to 85.1%. A number of 50 subjects is adequate to achieve 80% statistical power under a type one error rate 0.025 one-sided. The power analysis is based on simulation, 10000 iterations are carried out, Greenwood's method is applied.

Conditions

Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental arm

Endoscopic resection+ concurrent chemoradiotherapy

Group Type: EXPERIMENTAL

Intensity modulated radiotherapy (IMRT)

Intervention Type: PROCEDURE

Intensity-modulated radiation therapy (IMRT) with a total dose of 45Gy in 25 fractions

Chemotherapy

Intervention Type: DRUG

Nedaplatin 25 mg/m2 and Paclitaxel liposome 45mg/m2, day 1, every week, 5 weeks

Interventions

Intensity modulated radiotherapy (IMRT)

Intensity-modulated radiation therapy (IMRT) with a total dose of 45Gy in 25 fractions

Intervention Type: PROCEDURE

Chemotherapy

Nedaplatin 25 mg/m2 and Paclitaxel liposome 45mg/m2, day 1, every week, 5 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female patients aged 18 to 75 years (18 years and 75 years are inclusive).
• The Eastern Cooperative Oncology Group (ECOG) performance status score is 0 to 1 point.
• Weight loss (intentional or unintentional) of less than or equal to 10% of body weight in the 6 months prior to surgery.
• Complete radiological staging is required before ER, including gastroscopy, endoscopic ultrasonography, chest CT, brain MRI and bone scan (if positive, bone metastasis must be confirmed by MRI or CT examination of corresponding parts, otherwise bone metastasis cannot be determined). No lymph nodes with shorter diameter >10mm in mediastinum presented by endoscopic ultrasonography or chest CT. No abdominal nor neck lymph node metastases presented by B-ultrasound.
• Primary lesion located in thoracic esophagus.
• Clinical stage: cT1（sm1/sm2）N0M0 (The 8th edition of American Joint Committee on Cancer [AJCC]) before ER.
• ER is a complete removal of tumor.
• Pathologically confirmed squamous cell carcinoma.
• Histologically confirmed diagnosis of T1a with LVI, T1b（sm1/sm2）with/without LVI, or microscopically positive vertical resection margin (R1 resection).
• Less than three endoscopically resected synchronous lesions with high risk factors (lymphovascular or mucous membrane invasion, submucous infiltration, poor differentiation or microscopically positive vertical resection margin), which can be safely encompassed in a tolerable radiation plan.
• Non-pregnancy and non-pregnancy plan in the next 12 months (urine pregnancy test or blood pregnancy test is required for women of childbearing age to exclude pregnancy).
• No serious medical disease nor organ dysfunction. Adequate BM, liver, kidney and heart function.
• Meet the treatment and follow-up criteria, able to receive treatment, follow-up and pathological examination. The subject has voluntarily signed the written informed consent form (ICF).

Exclusion Criteria

• Any positive N or M stage.
• Macroscopic residual tumor (R2 resection).
• Lesions with poor prognistic factors (lymphovascular or mucous membrane invasion, submucous infiltration, poor differentiation or microscopically positive vertical resection margin) solely resected endoscopically more than six months before evaluation.
• Patients with other malignant tumors within 5 years before enrollment.
• Unavailable gastroscope due to esophageal stenosis.
• Previously received electrocoagulation, other treatments (including photodynamic therapy, multipolar electrocoagulation, argon plasma coagulation, laser therapy, et al.) or radiotherapy.
• Previously received any esophageal surgery, excluding fundoplication with no complications (no slippage, dysphagia, et al.).
• Uncontrolled coagulation disorders: INR >2 or PLT<75,000/μL.
• Patients who are taking or have taken (within 7 days before/after treatment) aspirin, clopidogrel or other non-steroidal anti-inflammatory drugs.
• Patients with history of uncontrolled drug or alcohol dependence that limits the ability to understand or comply with medical orders, including inability to understand and execute ICF, post-treatment orders, or follow-up guidelines.
• Patients implanted pacemakers, including AICD, nerve stimulator or cardiac pacemaker, without the permission from specialist in charge.
• Patients with mental disease, serious medical disease or major organ dysfunction.
• Pregnant, lactating women or women without offspring.
• Patients unable to understand/express informed or consent.
• Patients with known allergy to platinum compounds or paclitaxel.
• Other circumstances which are considered by the investigator that the subject is unsuitable to be enrolled

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Zhouguang Hui, M.D.

Chief physician, Director of VIP Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhouguang Hui, M.D.

Role: CONTACT

drhuizg@163.com

8610-87787230

Facility Contacts

Zhouguang Hui, M.D.

Role: primary

drhuizg@163.com

8610-87787230

Other Identifiers

19/313-2097

Identifier Type: -

Identifier Source: org_study_id