Pembrolizumab Plus CRT Followed by Surgery in Upper ESCC

A Prospective, Single-arm Phase Ib/II Study to Explore the Safety and Efficacy of Pembrolizumab Combined With Neoadjuvant Chemoradiotherapy (CRT) Followed by Surgery for Upper Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)

Through a prospective, single-center, single-arm, phase Ib/II study, we aim to explore the safety and feasibility of a new treatment mode for upper esophageal cancer, which is that pembrolizumab combined with chemoradiotherapy as neoadjuvant therapy and then followed by radical surgery.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab

Detailed Description

Treatment includes induction treatment, sequential treatment and maintenance treatment.

1. Preoperative neoadjuvant therapy 1) Induction therapy (2 cycles): Immunotherapy+Chemotherapy Pembrolizumab 200mg, IV, D1, q3w, Albumin paclitaxel, 125mg/m2, IV, D1/D8, q3w; Cisplatin, 70mg/m2 in total, IV, given in three times, q3w. 2) Sequential treatment: Immunotherapy+Chemoradiotherapy Pembrolizumab 200mg, IV, D1, q3w, 2 cycles; Albumin paclitaxel, 100mg, IV, D1, QW, 4 cycles; Cisplatin, 20mg/m2, IV, D1, QW, 4 cycles. Radiotherapy: PTV: 44gy/2gy/22fx, 5 days a week, 5 weeks in total.
2. Surgery 4-8 weeks after the end of the neoadjuvant therapy, the operation can be performed only when the indexes of leukocyte, platelet, liver and kidney function of the patient are normal. The operation aims to achieve R0 resection with laryngeal preservation.
3. Postoperative adjuvant treatment Patients who did not reach pCR after operation were given pembrolizumab 200mg, IV, D1, q3w 4-6 weeks after operation until 1 year, disease progression or intolerable toxicity.
4. Follow-up period Patients will be continuously monitored during the study. The enrolled subjects will be closely followed up for 2 years.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yong Li, MD; Phone Number: +8613831120879; Email: liyongdoctor@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      • Contact: Yong Li, MD; Phone Number: +8613831120879; Email: liyongdoctor@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sign the informed consent form before enrollment;
2. Be aged 18-80 years old, and be male or female;
3. Have potentially upper ESCC (upper edge of tumor ≤ 5cm from esophageal entrance) diagnosed with cT1-3N1-2M0 or cT2-3N0M0 (AJCC 8th);
4. Have an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;
5. No previous treatments;
6. Be eligible for R0 resection before treatment;
7. Demonstrate adequate organ function; all screening laboratory tests will be performed within 10 days of treatment initiation;
8. Have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication if they are a female subject with childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
9. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. "Newly obtained" is defined as a specimen obtained up to 4 weeks (28 days) before the initiation of treatment on Day 10. Subjects for whom newly obtained samples cannot be provided (e.g., as newly obtained sample is inaccessible or due to subject safety concerns) may submit an archived specimen, but only with the agreement of the sponsor;

11. Be expected to survive >6 months; 12. Join the clinical study on a completely voluntary basis, demonstrate good adherence, and cooperate with the follow-up assessments for safety and survival

Exclusion Criteria:

1. Have undergone any previous therapy (e.g., an operation, radiotherapy, immunotherapy, or chemotherapy) for ESCC;
2. Have a history of other malignant tumor;
3. Be ineligible or have a contraindication for esophagectomy;
4. Have a history of other anti-PD-1/PD-L1 therapies, or have a known history of an allergy to macromolecular protein preparations or any component of PD-1;
5. Have a diagnosis of immunodeficiency or have received chronic systemic steroid therapy (in doses >10 mg daily of a prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of the study drug;
6. Have an active autoimmune disease that required systemic treatment in the past 2 years (e.g., the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs);
7. Have poorly controlled cardiac symptoms or cardiac diseases;
8. Have a history or evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severely impaired lung function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Experimental arm; Immunotherapy combined with chemotherapy and radiotherapy

Drug: Pembrolizumab; The subjects first receive induction therapy with pembrolizumab combined with chemotherapy for 6 weeks, and then receive sequential therapy with pembrolizumab combined with concurrent chemoradiotherapy for 6 weeks, and receive surgical treatment within 4-8 weeks after neoadjuvant therapy. For patients whose postoperative pathology is confirmed as PCR (pathological complete response), the patients will be observed with long-time follow-up; If the postoperative pathology is confirmed as non-PCR, pembrolizumab will be administrated until 1 year or disease progression or intolerable toxicity.; Other Names: IO combined therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response	Viable tumor comprised ≤ 10% of resected tumor specimens	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from the enrollment to death of any cause	24 months
R0 resection rate	R0 resection rate	At time of surgery
Larynx preservation rate	Larynx preservation rate	At time of surgery
Disease-free survival (DFS)	DFS is defined as the time interval between the date of enrollment and the date of the first documented evidence of relapse after radical resection at any site or death related to cancer (including toxicity), whichever occurred first.	24 months
Local-regional recurrence free survival (LRRFS)	LRRFS is defined as the time interval between the date of enrollment and the date of the first documented evidence of local-regional relapse after radical resection at primary site or death related to cancer (including toxicity), whichever occurred first.	24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2022
• Primary Completion (ANTICIPATED): December 1, 2023
• Study Completion (ANTICIPATED): December 1, 2024

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (ACTUAL): September 15, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: August 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: Upper EC program

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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