Carrelizumab Combined With Concurrent Radiotherapy and Chemotherapy for Unresectable Esophageal Squamous Cell Carcinoma

NCT06048926 | Enrolling By Invitation

• 1 other identifier: GXL-004
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, double-blind, placebo-controlled, multicenter phase III clinical study to evaluate the efficacy and safety of carrelizumab plus concurrent chemoradiotherapy compared with placebo plus concurrent chemoradiotherapy in the treatment of patients with inoperably advanced esophageal cancer, and to explore the relationship between PD-L1 expression and efficacy in tumor tissues. Experimental group: carrelizumab in combination with concurrent chemoradiotherapy PD-1: carrelizumab: 200 mg/3W Chemotherapy: Paclitaxel: 50 mg/m2/W Cisplatin: 25mg/m2/W Radiotherapy: 50.4 Gy / 28 f Chemotherapy drugs are used for 5 cycles, and carrelibizumab is used for up to 24 months until PD or is intolerable Control group: placebo-resistant in combination with chemoradiotherapy placebo: 200 mg/3 W Chemotherapy: Paclitaxel: 50 mg/m2/W Cisplatin: 25mg/m2/W Radiotherapy: 50.4 Gy / 28 f Chemotherapy drugs are used for 5 cycles, and carrelibizumab is used for up to 24 months until PD or is intolerable

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Carrelizumab; Concurrent chemoradiotherapy; Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• PFS evaluated by IRC

  IRC stands for Independent Review Committee Assessment，Progression-free disease as assessed by an independent review committee Progression-free survival refers to the time from randomization to the first occurrence of disease progression or death from any cause

  up to 2 years

Secondary Outcomes (3)

• OS Overall Survival

  up to 2 years

• ORR

  through study completion, an average of 18 month

• Progression-free survival evaluated by Researchers

  up to 2 years

Study Arms (2)

Experimental group: carrelizumab in combination with concurrent chemoradiotherapy

EXPERIMENTAL

Study drugs were administered intravenously on the first day of each cycle. Administered sequentially: carrelizumab, 200mg/time, paclitaxel, 50mg/m2, cisplatin, 25mg/m2, chemotherapy once a week, a total of 5 doses, carrelizumab every three weeks until PD or intolerable, up to 2 years, simultaneous radiotherapy at the first dose, the total dose of radiotherapy is 50.4Gy, completed in 28 divided doses, 1.8Gy each time, 5 times a week.

Drug: Carrelizumab; Drug: Paclitaxel injection; Drug: Cisplatin; Radiation: Concurrent chemoradiotherapy

Control group: placebo-resistant in combination with chemoradiotherapy

PLACEBO COMPARATOR

Placebo: 200 mg intravenously given with Q3W until PD or intolerable, carrelizumab/placebo for up to 2 years. Paclitaxel: 50mg/m2, iv, D1, 8, 15, 22, 29, once a week, a total of 5 times. cisplatin: 25mg/m2,iv, D1, 8, 15, 22, 29, once a week, a total of 5 doses. Radiotherapy: total dose of 50.4 Gy, completed in 28 divided doses of 1.8 Gy each time, 5 times a week.

Drug: Paclitaxel injection; Drug: Cisplatin; Radiation: Concurrent chemoradiotherapy

Interventions

Carrelizumab DRUG

200 mg/time, iv, Q3W

Also known as: Erica

Experimental group: carrelizumab in combination with concurrent chemoradiotherapy

Paclitaxel injection DRUG

50mg/m2,iv, D1, 8, 15, 22, 29, once a week, a total of 5 times

Also known as: chemotherapy

Control group: placebo-resistant in combination with chemoradiotherapy; Experimental group: carrelizumab in combination with concurrent chemoradiotherapy

Cisplatin DRUG

25mg/m2，iv， D1、8、15、22、29，once a week, a total of 5 times

Also known as: chemotherapy

Control group: placebo-resistant in combination with chemoradiotherapy; Experimental group: carrelizumab in combination with concurrent chemoradiotherapy

Concurrent chemoradiotherapy RADIATION

Radiotherapy was given simultaneously at the time of the first dose, and the total dose of radiotherapy was 50.4 Gy, which was completed in 28 divided doses of 1.8 Gy each time, 5 times a week.

Also known as: Radiotherapy

Control group: placebo-resistant in combination with chemoradiotherapy; Experimental group: carrelizumab in combination with concurrent chemoradiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients voluntarily participate in this study and sign informed consent;
• Age 18-75 years, including 18 and 75 years old, male or female;
• Patients with histologically confirmed locally advanced esophageal squamous cell carcinoma with a clinical stage of stage II-IVa that is inoperably resectable (including unresectable, or has contraindications to surgery or refuses surgery) (according to the 8th edition AJCC stage, the pre-treatment clinical stage is: cT1N2-3M0, cT2-4bN0-3M0);
• the presence of measurable and/or non-measurable lesions that meet the definition of the Efficacy Evaluation Criteria for Solid Tumors (RECIST1.1);
• Have not received systemic antineoplastic therapy (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biological therapy, topical therapy, and other investigational therapies)
• ECOG: 0\~1 point
• Fresh or archived tumor tissue samples within 6 months (fresh samples preferred) must be provided for biomarker (such as PD-L1) analysis, the sample type is FFPE tumor tissue block or at least 5 unstained, 3-5 μm thick FFPE tumor tissue section, for subjects who cannot provide tissue samples that meet the above requirements, they can discuss with the sponsor to determine whether to enroll;
• Expected survival≥ 3 months;
• The function of vital organs meets the following requirements (no blood components and cell growth factors are allowed 2 weeks before starting screening tests):
• Absolute neutrophil count (ANC) ≥1.5×109/L;
• platelets≥ 100×109/L;
• hemoglobin≥ 9g/dL;
• serum albumin≥ 2.8 g/dL;
• Total bilirubin ≤ 1.5 × ULN, ALT, AST and/or AKP≤2.5 × ULN;
• Serum creatinine ≤1.5 × ULN or creatinine clearance ≥ 60 mL/min (calculated according to the Cockcroft-Gault formula, see Annex II);

You may not qualify if:

• history of surgery for esophageal cancer;
• history of previous fistula due to primary tumor invasion;
• a higher risk of gastrointestinal bleeding, esophageal fistula, or esophageal perforation;
• participants with poor nutritional status with a BMI of less than 18.5 kg/m2 or a PG-SGA score of ≥9;
• have undergone major surgery or severe trauma within 4 weeks prior to the first use of the study drug;
• presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Have received or are currently receiving any of the following treatments:
• Anti-PD-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy;
• Have received any investigational drug within 4 weeks prior to the first use of the investigational drug;
• Participants who require systemic therapy with corticosteroids (\> 10 mg prednisone equivalent per day) or other immunosuppressants within 2 weeks prior to the first study drug, except for local inflammation of the esophagus and for the prevention of allergies and nausea and vomiting. In other special circumstances, it is necessary to communicate with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroid replacement and adrenocorticosteroid replacement at a dose \> a potent dose of 10 mg/day prednisone is allowed;
• Those who have received an antitumor vaccine or have received a live vaccine within 4 weeks prior to the first dose of the study drug
• have any active autoimmune disease or history of autoimmune disease (eg, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary physitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism); Except vitiligo or patients with asthma/allergies of the same age who have recovered and do not require any intervention in adulthood; Patients with autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone and type I diabetes mellitus treated with stable doses of insulin may be included;
• a history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation;
• Subjects with uncontrolled cardiac clinical symptoms or diseases, such as (1) heart failure with NYHA II and above, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
• Severe infection (CTC AE\> grade 2) within 4 weeks prior to the first use of the study drug, such as severe pneumonia, bacteremia, infection comorbidities, etc. requiring hospitalization; Baseline chest imaging suggests active lung inflammation, signs and symptoms of infection present in the 2 weeks prior to first study drug use requiring oral or intravenous antibiotic therapy, except for prophylactic antibiotics;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, China

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

camrelizumab; Paclitaxel; Drug Therapy; Cisplatin; Chemoradiotherapy; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Combined Modality Therapy

Study Officials

• Xiaolin MM GE

  The First Affiliated Hospital with Nanjing Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2023
• First Posted: September 21, 2023
• Study Start: July 30, 2022
• Primary Completion: July 30, 2025
• Study Completion (Estimated): July 30, 2028
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)