Camrelizumab Combined With Neoadjuvant Concurrent Chemoradiotherapy for Resectable Locally Advanced ESCC（NICE-RT）

A Single-arm，Single-center，Phase II Trial of Camrelizumab Combined With Neoadjuvant Concurrent Chemoradiotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma（NICE-RT）

NICE-RT study is a "safety run-in" and phase II trial evaluating the safety and efficacy of Camrelizumab combined with Nab-paclitaxel and Carboplatin and Radiotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Chemotherapy (nab-paclitaxel AUC=2 and carboplatin 80mg/m2)，Immunotherapy (camrelizumab 200mg)、Radiotherapy(primary lesion and adjacent lymph nodes 41.4Gy， distant lymph node 0.5Gy*4)

Detailed Description

Considering that immunotherapy combined with concurrent chemoradiotherapy may have unknown AEs, in order to explore the safety and tolerability of the regimen of camrelizumab combined with nab-paclitaxel and carboplatin and radiotherapy, this study set up an initial "safety run-in" phase. 10 patients will be firstly enrolled, and treatment-related adverse reactions（TRAEs）and surgical complications will be observed at the same time. If the completion rate of neoadjuvant therapy and surgery is greater than 80%, rate of 30-day major complication is less than 20%,and no death, it will continue to enroll 40 patients to explore the efficacy and safety of the regimen. If the completion rate of neoadjuvant therapy and surgery is less than 80%, the MDT will determine whether the study move forward. If treatment related death is more than 1 patients, the study will be terminated.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jun Liu, M.D.; Phone Number: 3602 +862122200000; Email: drjunliu@qq.com
• Study Contact Backup: Name: Xiaolong Fu, M.D.; Phone Number: 3602 +862122200000

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital
      • Contact: Jun Liu, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent has been signed.
2. In age from 18 to 75.
3. Thoracic esophageal squamous cell carcinoma confirmed by histology or cytology, which is classified as cT1b-4aN2-3M0 or M1 (only for supraclavicular lymph node metastasis), accompanied by lymph node metastasis (CT shows that the short diameter of the lymph node is greater than 1cm, the lymph node near the recurrent laryngeal nerve is greater than 8mm, the lymph node in the left upper abdominal region of the stomach is greater than 8mm, and PET-CT indicates positive).
4. At least one metastatic lymph node is more than or equal to 5cm from the primary lesion.
5. Have not received any anti-tumor treatment for esophageal cancer in the past, including radiotherapy, chemotherapy, surgery, etc.
6. The investigator assessed that lesion can be removed surgically.
7. At least one measurable lesion (according to RECIST 1.1)
8. ECOG PS: 0~1.
9. Weight loss<10% within 3 months, PG-SGA score<8.
10. Has sufficient organ function within 28 days before the first administration, (1) Blood routine: WBC≥3.0×109/L; ANC≥1.5×109/L; PLT≥50×109/L; HGB≥90 g/L (2) Liver function: AST≤5.0×ULN; ALT≤5.0×ULN; TBIL≤2.0×ULN (3) Renal function: Cr≤1.5×ULN or CrCl ≥60 mL/min (4) Coagulation function: INR≤1.5; APTT≤1.5×ULN (5)Women of childbearing age must take contraceptive measures within 3 months from the first dose to the last use of the study drug.

Exclusion Criteria:

1.Pathological type and stage

1. Pathology indicates that it is mixed squamous cell carcinoma (including adenosquamous carcinoma, squamous cell carcinoma, small cell carcinoma, carcinosarcoma, sarcomatoid carcinoma, etc.)
2. Non resectable or metastatic esophageal cancer

2. Medical history and complications

1. Subjects with any known active autoimmune disease (subjects who have stable clinical symptoms and do not need systematic use of immunosuppressants, such as type I diabetes and hypothyroidism that only need hormone treatment, and skin diseases that do not need systematic treatment can be included).
2. Subjects who have any complications requiring systemic treatment with glucocorticoids such as prednisone (>10mg/day) or who have used immunosuppressive drugs within 14 days before the first administration (subjects who do not have active autoimmune diseases, inhale or locally use glucocorticoids, and who use prednisone (>10mg/day) for hormone replacement treatment of adrenal insufficiency can be included in the group).
3. Subjects have received tumor vaccine or other immune activated anti-tumor drugs (such as interferon, interleukin, thymosin or immunocyte therapy) within 1 month before the first administration.
4. The subject is participating in other clinical trials or has received drug intervention from other clinical trials within 4 weeks before the first administration.
5. Subjects had received surgery or radiotherapy>30Gy within 4 weeks before the first administration.
6. Subjects with other malignant tumors that need to be treated (subjects with skin basal cell carcinoma, skin squamous cell carcinoma, breast cancer in situ or cervical cancer in situ that have received radical treatment and do not need other treatment can be included)
7. Subjects have suffered from serious cardiovascular diseases in the past: myocardial ischemia or myocardial infarction above Grade II, arrhythmia under poor control (including QTc interval ≥ 480 ms); Grade III-IV cardiac insufficiency; Color Doppler echocardiography showed that left ventricular ejection fraction (LVEF) was less than 50%.
8. Subjects have known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
9. Subjects received live vaccine within 30 days before the first administration.

3. Laboratory inspection

1. The subject's serum is HIV positive
2. Active hepatitis B (HbsAg positive and HBV-DNA ≥ 103 copies/mL) or active hepatitis C (HCV antibody positive and HCV-DNA positive, requiring antiviral treatment at the same time).

4. Allergies and adverse drug reactions should be excluded

1. Presence of allergy or hypersensitivity to monoclonal antibodies
2. Allergy or intolerance during infusion

5. Diseases or abnormal laboratory indicators that the investigator believes will affect the research results or are not in line with the interests of the subject should be excluded.

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: Immunotherapy combined with Chemoradiotherapy; A:Chemotherapy: nab-paclitaxel (80mg/m2), carboplatin (AUC=2)，on day 1,8,15,22,29; B:Immunotherapy: camrelizumab (200mg)，IV on days 5 and 26; C:Radiotherapy: Primary lesion and adjacent lymph nodes: 41.4Gy, 1.8Gy/23f; Abscopal lymph node 2Gy, 0.5Gy/4f. D:Ivor-Lewis or McKeown esophagectomy The participants will receive preoperative A+B+C. 4-6 weeks after completion of preoperative therapy ，D will be performed if there is no contraindication.

Drug: Chemotherapy (nab-paclitaxel AUC=2 and carboplatin 80mg/m2)，Immunotherapy (camrelizumab 200mg)、Radiotherapy(primary lesion and adjacent lymph nodes 41.4Gy， distant lymph node 0.5Gy*4); Neoadjuvant treatment period:Radiotherapy: Primary lesions and adjacent lymph nodes: The mode of involved field irradiation (IFI) is adopted, no preventive radiation is given. The total dose is 41.4Gy, 1.8Gy/23f. Distal lymph nodes ≥ 5cm away from the primary lesion: low-dose radiotherapy with a total dose of 4Gy, 0.5Gy/8f, Day1 to Day4, Day22 to Day25.Chemotherapy: Carboplatin(AUC=2), Nab-paclitaxel(80mg/m2), Day1/8/15/22/29. Immunotherapy: Camrelizumab(200mg, Day5, Day26).; Perioperative period:Undergo surgery within 4-6 weeks after neoadjuvant therapy; Adjuvant treatment period: Camrelizumab: (200mg, Q3W)，continued for up to 1 years，until PD or intolerable toxicity.; Other Names: Camrelizumab: ai rui ka, SHR-1210; Nab-paclitaxel: ai yue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety(The rates of grade 3 and higher-grade treatment-related adverse events)	Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported	From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose
pCR	pathological complete response (pCR) is defined as disappearance of all invasive cancer after completion of neoadjuvant chemotherapy	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR	major pathologic response (MPR) is defined as residual viable tumor of less than or equal to 10%	12 months
ORR	objective response rate (ORR) is defined as the proportion of patients with a complete response(CR) or partial response(PR) to treatment according to RECIST v1.1	12 months
EFS	event-free survival (EFS) is defined as the time after treatment that a group of people in a clinical trial has not had cancer come back or get worse	12 months
OS	overall survival (OS) is defined as the time from treatment to death, regardless of disease recurrence	12 months

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital
• Investigators: Principal Investigator: Jun Liu, M.D., Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 25, 2022
• Primary Completion (Anticipated): December 25, 2023
• Study Completion (Anticipated): December 25, 2024

Study Registration Dates

• First Submitted: November 24, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: NICE-RT

Drug and device information, study documents

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