Trial Title:
Pembrolizumab Plus CRT Followed by Surgery in Upper ESCC
NCT ID:
NCT05541445
Condition:
Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
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.
Arm group label:
Experimental arm
Other name:
IO combined therapy
Summary:
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.
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Address:
City:
Beijing
Zip:
100021
Country:
China
Status:
Recruiting
Contact:
Last name:
Yong Li, MD
Phone:
+8613831120879
Email:
liyongdoctor@126.com
Start date:
August 1, 2022
Completion date:
December 1, 2024
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05541445
