Clinical trial NCT04278287: Chemoradiotherapy in Unresectable Esophageal Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Chemoradiotherapy
Albumin-bound Paxlitaxel
Unresectable Malignant Neoplasm
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2020-02-20
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Local control rate
timeFrame: 1 year from the start of treatment to tumor recurrence
Secondary outcomes:
measure: Number of participants with acute toxicities
timeFrame: 10 week, from the start of treatment to 1 month after chemoradiotherapy
measure: Objective response rate
timeFrame: 5.5 week
measure: Disease Free Survival
timeFrame: 1 year, 2 year
measure: Progression Free Survival
timeFrame: 1 year, 2 year
measure: Overall Survival
timeFrame: 1 year, 2 year
measure: Radiomics analysis
timeFrame: 5.5 week
measure: ctDNA analysis
timeFrame: 4 week, 2 month, 1 year, 2 year
Other outcomes:
Locations:
city: Anyang
country: China
facility: Department 4th of Radiation Oncology, Anyang Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
state: Hunan
city: Nanjing
country: China
facility: Department of Radiation oncology, Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Research/The affiliated Cancer Hospital of Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: Department of Radiation oncology, Jiangsu Province Hospital/The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
city: Beijing
country: China
facility: 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)
Study officials:
affiliation: Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
name: Xin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: