PALACE: Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus
Study Details
Study Description
Brief Summary
This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Esophageal cancer ranks the eighth most common cancer (the fifth most common cancer in China), while ESCC is the most common subtype in Asia (more than 90 % in china). Radical resection is thought to be the mainstay of esophageal cancer treatment and preoperative CRT is well applied in treating locally advanced esophageal cancer. In a multicohort, phase IB study, pembrolizumab was used in 23 unresectable esophageal cancer patients. In this clinical trial, the incidence of grade 3 treatment-related adverse events was 39 % without the appearance of grade 4 and higher-grade adverse event, while the overall response rate reached 30 %. The safety of immune checkpoint therapy for unresected esophageal cancers using nivolumab, a different PD-1 monoclonal antibody, has also been confirmed by high quality clinical trials.
This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1 Arm 1:preoperative pembrolizumab with chemoradiotherapy group Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 15 and 29. Surgery will be performed within 6 weeks after completion of preoperative therapy described above. |
Drug: Pembrolizumab
Arm1：Pre-operative Pembrolizumab+chemoradiotherapy
Other Names:
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Outcome Measures
Primary Outcome Measures
- Safety(The rates of grade 3 and higher-grade treatment-related adverse events) [From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose]
Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported
Secondary Outcome Measures
- Feasibility (The rates of patients who finished pembrolizumab with chemoradiotherapy and receive surgery within 6 weeks after preoperative therapies.) [From date of treatment allocation until surgery or definitive chemoradiotherapy was applied,whichever came first, assessed up to 5 months]
Feasibility was defined as completion of surgery within 6 weeks after preoperative therapies.
- Pathologic complete response [From date of treatment allocation and during treatment period up to 1 year]
Pathologic complete response was defined as pT0N0M0
- Radiographic response [From date of treatment allocation and during treatment period up to 3 months]
To assess radiographic response to neoadjuvant pembrolizumab with concurrent chemoradiotherapy using RECIST 1.1.
Eligibility Criteria
Criteria
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 2. Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications 3. Subjects with a history of symptomatic interstitial lung disease 4. History of allergy to study drug components 5. Women must not be pregnant or breast-feeding 6. Men with female partners (WOCBP) that are not willing to use contraception 7. Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for any other past malignancy
- Underlying 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ruijin Hospital, Shanghai JiaoTong University School of Medicine | Shanghai | Shanghai | China | 200025 |
Sponsors and Collaborators
- Hecheng Li M.D., Ph.D
Investigators
- Principal Investigator: Hecheng Li, MD PHD, Ruijin Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RuijinH-nit