Chemoradiotherapy in Unresectable Esophageal Cancer

A Phase I/II Study of Chemoradiotherapy Using Albumin-Bound Paclitaxel and Cisplatin in Unresectable Esophageal Squamous Cell Carcinomas Based on Nutritional Risk Screening Score (NRS2002)

This phase I/II clinical study is designed to evaluate the 1 year local tumor control rate of chemoradiotherapy using albumin-bound paclitaxel and cisplatin in unresectable esophageal squamous cell carcinomas based on Nutritional Risk Screening NRS2002.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer; Unresectable Malignant Neoplasm; Chemoradiotherapy; Albumin-bound Paxlitaxel
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Albumin-Bound Paclitaxel; Drug: Cisplatin

Detailed Description

This Phase I/II clinical study is meticulously designed to assess the one-year local tumor control rate of a chemoradiotherapy regimen that combines albumin-bound paclitaxel and cisplatin in patients with unresectable esophageal squamous cell carcinoma (ESCC). The selection of participants is guided by the Nutritional Risk Screening (NRS2002) tool, which ensures that nutritional risk factors are adequately considered and managed throughout the study.

The trial will enroll patients diagnosed with unresectable ESCC, a condition where surgical intervention is not feasible due to the tumor's location, size, or patient comorbidities. Participants will undergo a thorough nutritional assessment using the NRS2002 criteria, which evaluates factors such as weight loss, body mass index, dietary intake, and severity of disease to determine their nutritional risk score. This screening is crucial as it helps identify patients who may benefit from nutritional interventions, which could potentially improve their overall response to the treatment and quality of life.

Once enrolled, patients will receive a combination chemoradiotherapy of albumin-bound paclitaxel and cisplatin. Albumin-bound paclitaxel is chosen for its ability to improve the delivery and efficacy of paclitaxel, a chemotherapy drug, by enhancing its solubility and distribution within the body. Cisplatin, a platinum-based chemotherapy agent, is included due to its well-established efficacy in treating various cancers, including esophageal cancer. This combination aims to maximize tumor reduction while managing potential side effects.

The primary endpoint of the study is to determine the local tumor control rate at one year, which refers to the percentage of patients whose tumors have not progressed or recurred within the treated area during this period. Secondary endpoints include overall survival, progression-free survival, and assessment of treatment-related toxicity. Additionally, the study will monitor changes in patients' nutritional status and quality of life, aiming to provide comprehensive insights into the efficacy and safety of this chemoradiotherapy regimen.

Regular follow-ups and imaging studies, such as CT scans or PET scans, will be conducted to evaluate the tumor response and detect any signs of progression. Blood tests and other laboratory assessments will be performed periodically to monitor patients' overall health and manage any adverse effects promptly. The data collected from this study will contribute valuable information to the ongoing efforts to improve treatment outcomes for patients with unresectable esophageal squamous cell carcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xin Wang, MD; Phone Number: +861013311583220; Email: beryl_wx2000@163.com

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)
    • Contact: Xin Wang, MD; Phone Number: +861013311583220; Email: beryl_wx2000@163.com
  • Henan
    • Anyang, Henan, China, 455001
      • Recruiting
      • Department 4th of Radiation Oncology, Anyang Cancer Hospital
      • Contact: Xiaomin Wang, MD; Email: shine828@163.com
  • Hunan
    • Changsha, Hunan, China, 410031
      • Recruiting
      • Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
      • Contact: Qin Xiao, MD; Email: xiaoqin_200909@163.com
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Department of Radiation oncology, Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Research/The affiliated Cancer Hospital of Nanjing Medical University
      • Contact: Cheng Chen, MD
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Department of Radiation oncology, Jiangsu Province Hospital/The First Affiliated Hospital with Nanjing Medical University
      • Contact: Xiaolin Ge, MD; Email: doctorgxl@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18~75 years
• Pathologically or cytologically proven unresectable esophageal squamous cell carcinomas in patients staged as T3N1M0-1b and T4N0-1M0-1b(AJCC 6th TNM staging,M1b limited to clavicular or celiac lymph node metastasis)
• Primary treatment performed in Cancer Hospital, Chinese Academy of Medical Sciences
• ECOG PS score: 0~1
• NRS2002 score <3
• Estimated survival time ≥3 months
• Normal organ and marrow function as defined below:

Hemoglobin: greater than or equal to 100g/L ;Leukocytes: greater than or equal to 4,000 G/L; Neutrophil: greater than or equal to 2,000 G/L; Platelets: greater than or equal to 100,000/mm3 ; Creatinine: less than or equal to 1.5 times the upper limit or CCR greater than or equal to 60 ml/min; AST/ALT: less than or equal to 2.5 times the upper limit; Total bilirubin: less than or equal to 1.5 times the upper limit; INR: less than or equal to 1.5 times the upper limit; APTT: less than or equal to 1.5 times the upper limit; PT: less than or equal to 1.5 times the upper limit

• Informed consent

Exclusion Criteria:

• With any distant metastasis out of regional lymphatic drainage or in liver, lung, bone, CNS, etc
• Patients with other cancer history in 5 years except cervical carcinoma in situ and non-malignant melanoma skin cancer
• Existing active infection such as active tuberculosis and hepatitis
• History of myocardial infarction within the past 6 months or history of ventricular arrhythmia
• Uncontrolled illness including, but not limited to, active infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness
• History of allergic reactions attributed to paclitaxel, albumin or cisplatin
• Participation in other clinical trials currently or within 4 weeks of selection
• Pregnant or lactating females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Albumin-Bound Paclitaxel and Cisplatin based chemoradiotherapy; Chemoradiotherapy arm receives intensity-modulated radiation therapy, volume modulated arc therapy or tomotherapy concurrently with albumin-bound paclitaxel and cisplatin (weekly intravenous infusion in 5-6 weeks).	Radiation: Radiotherapy; 59.92Gy and 2.14Gy in 28 fractions to PGTV and 50.4Gy and 1.8Gy in 28 fractions 5 days every week in 5.5 weeks.; Drug: Albumin-Bound Paclitaxel; 100mg/d weekly,repeatedly on the first day,by intravenous infusion in 5-6 weeks.; Other Names: Nab-Paclitaxel; Drug: Cisplatin; 25mg/m2 weekly,by intravenous infusion in 5-6 weeks.; Other Names: platinum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control rate	Control rate of primary esophageal cancer and metastatic lymph nodes within irradiation fields	1 year from the start of treatment to tumor recurrence

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with acute toxicities	Acute toxicities are evaluated by NCI-CTC version 5.0	10 week, from the start of treatment to 1 month after chemoradiotherapy
Objective response rate	Objective Response Rate are evaluated by RECIST 1.1	5.5 week
Radiomics analysis	Radiomics analysis for tumor response and survival prediction with pre- and post-chemoradiotherapy based on MRI and CT simulation	5.5 week
ctDNA analysis	ctDNA analysis to monitor therapeutic efficacy including tumor response and survival outcome	4 week, 2 month, 1 year, 2 year
Disease Free Survival	The time from treatment to progression or death	1 year, 2 year
Progression Free Survival	The time from treatment to progression or death	1 year, 2 year
Overall Survival	The time from treatment to death from any cause	1 year, 2 year

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Xin Wang, MD, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms; Esophageal Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Paclitaxel
• Other Study ID Numbers: 19/325-2109

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No