An Organ Preservation Strategies After Chemoradiotherapy Combined With Immunotherapy for Esophageal Cancer (PALACE3). (PALACE3)

An Organ Preservation Strategies After Chemoradiotherapy Combined With Immunotherapy for Esophageal Cancer vs Cross Therapy.

Patients with locally advanced esophageal squamous cell carcinoma will randomly assigned to receive neoadjuvant chemo-radiotherapy combined with immunotherapy post organ preservation strategy (experimental group) or neoadjuvant chemo-radiotherapy followed by surgery (control group).

The 3-year overall survival rate is the primary outcome.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Combination product: Experimental: Arm 1 Organ preservation; Combination product: Active Comparator: Arm 2 Surgery

Detailed Description

The investigators will conduct the open, multicenter, prospective, randomized controlled clinical study(PALACE3). Patients with locally advanced esophageal squamous cell carcinoma will randomly assigned to either receive neoadjuvant synchronous radiotherapy and chemotherapy combined with immunotherapy followed by organ preservation strategy (experimental group, Arm1) or neoadjuvant concurrent radiotherapy and chemotherapy followed by radical surgery (control group,Arm 2). Collect relevant data on preoperative treatment, re examination after neoadjuvant therapy, perioperative and long-term follow-up of patients, and evaluate the clinical treatment effects (cCR rate), surgical pathological results (pCR rate, R0 resection rate, tumor regression grade, lymph node positivity rate), neoadjuvant therapy and perioperative complications, long-term oncological effects (total survival, disease-free survival), and quality of life of the two treatment plans through statistical analysis.

• Study Type: Interventional
• Enrollment (Estimated): 356
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chengqiang Li; Phone Number: 13524282905; Email: lcq12305@rjh.com.cn
• Study Contact Backup: Name: Hecheng Li; Phone Number: 19121652450; Email: lihecheng2000@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Ruijin Hospital
    • Contact: Chengqiang LI, MD/PHD; Phone Number: 19121652450
    • Contact: Yuqin Cao, MD/PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:

  • Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients approve and sign the informed consent

Exclusion Criteria:

• Patients with active autoimmune disease or history of autoimmune disease.
• Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications.
• Subjects with a history of symptomatic interstitial lung disease.
• History of allergy to study drug components.
• Women must not be pregnant or breast-feeding.
• Men with female partners (WOCBP) that are not willing to use contraception.
• Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for any other past malignancy.
• medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm1 Organ preservation; A: Camrelizumab 200mg IV on days 1 and 22 B: Carboplatin (AUC=2) IV and Paclitaxel-albumin (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. A+B+C=neoadjuvant therapy Patients will undergo clinical response evaluations (CREs) after neoadjuvant therapy(A+B+C）, If cancer is detected, surgery will be performed. Patients with clinical complete response （cCR） are eligible for active surveillance where regular CREs are performed to detect regrowth of cancer.Postoperative adjuvant therapy will follow the NCCN guideline.	Combination product: Experimental: Arm 1 Organ preservation; Arm 1 patients will undergo clinical response evaluations (CREs) after neoadjuvant therapy(A+B+C）, If cancer is detected, surgery will be performed. Patients with clinical complete response （cCR） are eligible for active surveillance where regular CREs are performed to detect regrowth of cancer.Postoperative adjuvant therapy will follow the NCCN guideline. A: Camrelizumab 200mg IV on days 1 and 22 B: Carboplatin (AUC=2) IV and Paclitaxel-albumin (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. A+B+C=Neoadjuvant therapy
Active Comparator: Arm 2 Surgery; A: Camrelizumab 200mg IV on days 1 and 22 B: Carboplatin (AUC=2) IV and Paclitaxel-albumin (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Oesophagectomy will be offered to patients without contraindication.Postoperative adjuvant therapy will follow the NCCN guideline.	Combination product: Active Comparator: Arm 2 Surgery; Arm 2 patients will undergo surgery after neoadjuvant therapy(B+C）.Postoperative adjuvant therapy will follow the NCCN guideline. B: Carboplatin (AUC=2) IV and Paclitaxel-albumin (50mg/m²) IV on day 1,8,15,22,29. C: Radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year overall survival rate	The proportion of patients who survived within 3 years from randomization	From date of randomization until the date of death from any cause，up to 5 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Hecheng Li, MD/PHD, Ruijin Hospital Shanghaijiaotong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 16, 2024
• First Submitted That Met QC Criteria: March 29, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 30, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Active surveillance; Chemoradiotherapy; Organ preservation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: RTS-022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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