A Phase II Clinical Study of Sintilimab Combined with Chemotherapy Followed by Concurrent Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma (ESCC) (NICE-CS)

NCT06709417 | Recruiting Phase 2

• 1 other identifier: NICE-CS
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, phase II clinical study designed to evaluate the efficacy and safety of sintilimab combined with chemotherapy, followed by sequential concurrent chemoradiotherapy as conversion therapy, in treatment-naïve esophageal squamous cell carcinoma (ESCC) patients with cT4bN-/+M0 and/or cTanyN+M0 staging (including those with extracapsular invasion of mediastinal lymph nodes).

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Outcome Measures

Primary Outcomes (1)

• 2-yr OS rate

  The percentage of people in the study who are alive two years after the start of treatment.

  24 months

Secondary Outcomes (6)

• R0 resection rate

  24 months

• pCR rate

  24 months

• MPR rate

  24 months

• EFS

  24 months

• OS

  24 months

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Eligible participants will first receive two cycles of sintilimab in combination with liposomal paclitaxel and cisplatin. After two cycles, an evaluation will be conducted. Patients deemed eligible for surgery will undergo surgical resection, followed by up to one year of adjuvant sintilimab. The necessity of postoperative adjuvant radiotherapy will be determined by the investigator. For patients deemed ineligible for surgery, concurrent chemoradiotherapy will be administered. Four weeks after the completion of concurrent chemoradiotherapy, a second surgical evaluation will be performed. Patients eligible for surgery at this stage will undergo surgical resection followed by adjuvant sintilimab treatment. Those who remain ineligible for surgery will continue sintilimab treatment after concurrent chemoradiotherapy.

Drug: Sintilimab; Drug: Chemotherapy; Radiation: radiotherapy

Interventions

Sintilimab DRUG

Sintilimab 200mg iv Q3W

Experimental Arm

Chemotherapy DRUG

Liposomal paclitaxel: 150mg/m2, Q3W + cisplatin: 75mg/m2, Q3W (combined with PD-1 therapy) Liposomal paclitaxel: 50mg/m2, Q3W + cisplatin: 20mg/m2, Q3W (combined with radiotherapy )

Experimental Arm

radiotherapy RADIATION

The total dose is 5040cCy in 28 fractions (5 days per week, 1.8 Gy/day).

Experimental Arm

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent prior to the initiation of any study-related procedures.
• Age: ≥20 years and ≤75 years, no gender restrictions.
• Diagnosed with esophageal squamous cell carcinoma (ESCC) based on histopathology and imaging, with clinical staging of cT4bN-/+M0 and/or cTanyN+M0 (extracapsular invasion of mediastinal lymph nodes).
• Thoracic segment esophageal squamous cell carcinoma.
• Primary lesion is inoperable or inoperable due to extracapsular invasion of mediastinal lymph nodes.
• ECOG performance status (PS) of 0-1.
• Estimated survival time ≥6 months.
• No prior antitumor therapy for esophageal cancer, including but not limited to chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
• At least one measurable lesion as per RECIST 1.1 criteria.
• No surgical contraindications based on preoperative evaluation of organ function.
• Adequate organ function
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within three days prior to receiving the first dose of study medication (Cycle 1, Day 1). If the urine pregnancy test result is inconclusive, a serum pregnancy test is required. Non-childbearing potential is defined as postmenopausal for at least one year, surgical sterilization, or hysterectomy.
• Participants of childbearing potential (male or female) must use highly effective contraception methods (with an annual failure rate \<1%) throughout the study and for 120 days after the last dose of the investigational drug or 180 days after the last dose of chemotherapy, whichever is longer.

You may not qualify if:

• Diagnosis of malignancies other than esophageal cancer within 5 years prior to the first dose of the investigational drug (excluding radically treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the lung, or T1a non-invasive adenocarcinoma).
• Patients with existing or high-risk tracheoesophageal or aortoesophageal fistulas.
• Presence of distant metastases.
• Current participation in an interventional clinical study or receipt of other investigational drugs or devices within 4 weeks prior to the first dose.
• Prior treatment with anti-PD-1, anti-PD-L1, or any other agents targeting stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137).
• Receipt of systemic antitumor traditional Chinese medicine or immunomodulatory drugs (including thymosin, interferon, or interleukin) within 2 weeks prior to the first dose, except for local use to control pleural effusion.
• Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs) within 2 years prior to the first dose, excluding replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency).
• Use of systemic corticosteroids (excluding nasal, inhaled, or other locally administered corticosteroids) or other immunosuppressive drugs within 7 days prior to the first dose, except for physiological doses of corticosteroids (≤10 mg/day prednisone or equivalent).
• History of allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Known hypersensitivity to active ingredients or excipients in the investigational product.
• Failure to recover adequately (≤Grade 1 or baseline) from prior therapy-induced toxicities and/or complications prior to initiating treatment (excluding fatigue or alopecia).
• Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive).
• Untreated active hepatitis B, defined as HBsAg positivity with HBV DNA levels exceeding the upper limit of normal (ULN) at the study center. Subjects meeting the following criteria are eligible: HBV DNA \<1000 copies/mL (200 IU/mL) prior to the first dose and on antiviral therapy during chemotherapy to prevent reactivation. Subjects with anti-HBc(+), HBsAg(-), anti-HBs(-), and negative HBV DNA do not require prophylactic antiviral therapy but need close monitoring for reactivation.
• Active hepatitis C infection, defined as HCV antibody positivity and HCV RNA levels above the lower limit of detection.
• Receipt of live vaccines within 30 days prior to the first dose (Cycle 1, Day 1), except for injectable inactivated influenza vaccines administered within 30 days prior to the first dose. Intranasal attenuated live influenza vaccines are not allowed.

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

sintilimab; Drug Therapy; 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)

Therapeutics

Central Study Contacts

Jun Liu

CONTACT

+862122200000; drjunliu@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: November 25, 2024
• First Posted: November 29, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)