## Protocol Section
### Identification Module
**NCT ID:** NCT06420908

**Brief Title:** Adebrelimab Combined With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma (ESCC)

**Official Title:** Induction Adebrelimab Combined With Chemotherapy Followed by Concurrent Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma (ESCC): A Prospective, Single-arm, Phase II Clinical Study

#### Organization Study ID Info
**ID:** ARL-ESCC-001
#### Organization
**Class:** OTHER
**Full Name:** Hebei Medical University Fourth Hospital
### Status Module
#### Completion Date
**Date:** 2027-05-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-05-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-30

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Hebei Medical University Fourth Hospital

#### Responsible Party

**Investigator Affiliation:** Hebei Medical University Fourth Hospital

**Investigator Full Name:** Jun wang

**Investigator Title:** Principal Investigator

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** This study aims to evaluate the efficacy and safety of induction Adebrelimab (anti-PD-L1 antibody) combined with chemotherapy, then guided by PET-CT assessment to change the following chemoradiotherapy regiment for locally advanced unresectable ESCC.

### Conditions Module

**Conditions:**

- Esophageal Squamous Cell Carcinoma

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** SUV (PETr) reduction \>35%

**Intervention Names:**

- Drug: Adebrelimab+TP/FP+ radiation therapy

**Label:** PET-CT responders

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** SUV (PETr) reduction ≤35%

**Intervention Names:**

- Drug: Adebrelimab+FP/TP+ radiation therapy

**Label:** PET-CT non-responders

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- PET-CT responders

**Description:** Induction stage：

Adebrelimab : 1200mg d1, iv, q3w TP : nab-paclitaxel paclitaxel 180mg/m2, or paclitaxel 135-175mg/m2, d1, iv; carboplatin AUC=5-6, d1, iv, q3w FP : fluorouracil 400mg/m2, 2400 mg/m2 (48 hours), d1; cisplatin 75mg/m2, d1, iv, q3w 2 cycles;

Treatment stage:

TP : nab-paclitaxel paclitaxel 60-70mg/m2, or paclitaxel 75mg/m2, d1, iv; carboplatin AUC=5, d1, iv, q3w FP : fluorouracil 300mg/m2/d, iv; cisplatin 75mg/m2, d1, iv, q3w Radiation therapy (50.4Gy-60Gy/28-33f);

Consolidation stage:

Adebrelimab: 1200mg d1, iv, q3w , until disease progression or unacceptable toxicity occurs.

**Name:** Adebrelimab+TP/FP+ radiation therapy

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- PET-CT non-responders

**Description:** Induction stage：

Adebrelimab : 1200mg d1, iv, q3w TP : nab-paclitaxel paclitaxel 180mg/m2, or paclitaxel 135-175mg/m2, d1, iv; carboplatin AUC=5-6, d1, iv, q3w FP : fluorouracil 400mg/m2, 2400 mg/m2 (48 hours), d1; cisplatin 75mg/m2, d1, iv, q3w 2 cycles;

Treatment stage: (switch to a different chemotherapy drug which not used during the earlier induction phase)

FP : fluorouracil 300mg/m2/d, iv; cisplatin 75mg/m2, d1, iv, q3w TP : nab-paclitaxel paclitaxel 60-70mg/m2, or paclitaxel 75mg/m2, d1, iv; carboplatin AUC=5, d1, iv, q3w Radiation therapy (50.4Gy-60Gy/28-33f);

Consolidation stage:

Adebrelimab: 1200mg d1, iv, q3w , until disease progression or unacceptable toxicity occurs.

**Name:** Adebrelimab+FP/TP+ radiation therapy

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Baseline to measured date of progression or death from any cause

**Measure:** Progression free survival (PFS)

**Time Frame:** evaluated in 24 months since the treatment began

#### Secondary Outcomes

**Description:** Baseline to measured stable disease

**Measure:** 1. Objective response rate (ORR)

**Time Frame:** tumor assessment every 6 weeks since the treatment began，up to 24 monthss

**Description:** The duration of overall response is measured from the time that measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented.

**Measure:** 2. Duration of Overall Response（DoR）

**Time Frame:** tumor assessment every 6 weeks since the treatment began，up to 24 months

**Description:** Baseline to measured date of death from any cause

**Measure:** 3. Overall survival (OS)

**Time Frame:** the first day of treatment to death or last survival confirm date,up to 24 months

**Description:** Toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. The number of Participants with adverse events will be recorded at each treatment visit.

**Measure:** 4. Adverse events

**Time Frame:** up to 24 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1.Age 18-75 years old, both men and women; 2.Histopathology confirmed as esophageal squamous cell carcinoma，stage II-IVa：T1N2-3M0，T2-4bN+M0； 3.If technically feasible, all patients are recommended to have local staging determined by endoscopic ultrasound (EUS); The endoscopic examination report or gastrointestinal (GI) clinical records should clearly indicate the T and N stages; Perform PET-CT examination; 4.Except for basal or squamous cell skin cancer, bladder cancer in situ or cervical cancer, there is no history of malignant tumor within 5 years; Patients with malignant tumors who have undergone surgical treatment in the past and those who have survived disease-free for more than 5 years meet the inclusion criteria; 5.Have not received any systemic anti-tumor treatment in the past (systemic chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) 6.According to RECIST 1.1, at least one measurable lesion; 7.ECOG: 0\~1; 8.Expected survival period ≥ 12 weeks; 9.Major organ function has to meet the following certeria:

1. Blood routine examination:

   1. HB≥90g/L;
   2. ANC ≥ 1.5 × 109 / L;
   3. PLT ≥ 100 × 109 / L;
2. Biochemical examination:

   1. ALT and AST \< 2.5×ULN;
   2. TBIL ≤ 1.5×ULN;
   3. Cr ≤ 1.5×ULN; 9. Left ventricular ejection fraction (LVEF) ≥50%; 11. Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; negative serum or urine pregnancy test within 7 days prior to study enrollment And must be non-lactating patients; males should agree to patients who must use contraception during the study period and within 6 months after the end of the study period; 12. Participants were willing to join in this study, and written informed consent, good adherence, cooperate with the follow-up.

Exclusion Criteria:

1. Previous history of esophageal cancer surgery；
2. Higher risk of esophageal perforation or fistula；
3. Received systemic immunosuppressive therapy within 14 days prior to the first study medication；
4. Known or suspected to have interstitial pneumonia; Other moderate to severe lung diseases that may seriously affect respiratory function;
5. The patient has any active autoimmune disease or history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, enteritis, systemic lupus erythematosus, rheumatoid arthritis; patients with vitiligo, Asthma has been completely relieved in childhood, and patients who do not need any intervention after adulthood can be included; asthma patients who require bronchodilators for medical intervention cannot be included);
6. Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥ 1000 copies/ml or 500IU/ml), hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the lower limit of detection of the analytical method)；
7. Within 6 months, cerebral vascular accidents (including transient ischemic attacks or symptomatic pulmonary embolism) occur;
8. History of cardiovascular disease with significant clinical significance, including but not limited to: (1) congestive heart failure (NYHA grade\>2); (2) Unstable angina pectoris; (3) Have experienced myocardial infarction within 3 months; (4) Any supraventricular arrhythmias or ventricular arrhythmias that require treatment or intervention;
9. Severe infections within 4 weeks before study drug administration, or active infection with CTCAE ≥ 2 grade treated with antibiotics within 2 weeks before study drug administration;
10. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
11. History of psychiatric drugs abuse and can't quit or patients with mental disorders;
12. The researchers think inappropriate.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** wangjunzr@163.com

**Name:** Jun Wang, Dr.

**Phone:** 13931182128

**Role:** CONTACT

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000018307

- Term: Neoplasms, Squamous Cell

- ID: D000004938

- Term: Esophageal Neoplasms

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000006258

- Term: Head and Neck Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000004935

- Term: Esophageal Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M5550

- Name: Carcinoma, Squamous Cell

- Relevance: HIGH

- As Found: Squamous Cell Carcinoma

- ID: M1733

- Name: Esophageal Squamous Cell Carcinoma

- Relevance: HIGH

- As Found: Esophageal Squamous Cell Carcinoma

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M20451

- Name: Neoplasms, Squamous Cell

- Relevance: LOW

- As Found: Unknown

- ID: M8088

- Name: Esophageal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M9348

- Name: Head and Neck Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8085

- Name: Esophageal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T2141

- Name: Esophageal Cancer

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000002294

- Term: Carcinoma, Squamous Cell

- ID: D000077277

- Term: Esophageal Squamous Cell Carcinoma

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M19537

- Name: Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M18650

- Name: Carboplatin

- Relevance: LOW

- As Found: Unknown

- ID: M8600

- Name: Fluorouracil

- Relevance: LOW

- As Found: Unknown

- ID: M231

- Name: Albumin-Bound Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M6182

- Name: Cisplatin

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
