Esophageal Squamous Cell Carcinoma
Conditions
Keywords
esophageal squamous cell carcinoma, neoadjuvant chemoradiotherapy, pembrolizumab, immune therapy, checkpoint inhibitor
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.
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.
Interventions
DRUGPembrolizumab
Arm1：Pre-operative Pembrolizumab+chemoradiotherapy
Sponsors
Hecheng Li M.D., Ph.D
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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 1 and 22. Surgery will be performed within 6 weeks after completion of preoperative therapy described above
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* A patient will be eligible for inclusion in this study only if ALL of the following criteria apply: 1. Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 3. Patients approve and sign the informed consent
Exclusion criteria
* 1\. 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 8. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (Number of Participants With 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 | The number of participants with grade 3 and higher-grade treatment-related adverse events. Adverse events were evaluated using CTCAE 4.0, grade 3 treatment-related adverse events and higher-grade adverse events were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility (Number of Participants Who Finished Pembrolizumab With Chemoradiotherapy and Receive Surgery Within 4-6 Weeks After Preoperative Therapies) | From date of treatment allocation until surgery or definitive chemoradiotherapy was applied, whichever came first, assessed up to 5 months | The number of participants who finished pembrolizumab with chemoradiotherapy and receive surgery within 4-6 weeks after preoperative therapies. |
| Pathologic Complete Response | Two weeks after surgery | Pathologic complete response was defined as the lack of all signs of cancer in tissue samples removed during surgery after treatment with pembrolizumab and chemoradiotherapy. |
| 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. Complete metabolic response (cMR), defined as a physiological distribution of FDG uptake on PET-CT with a SUVmax value of less than 4 with no nodal uptake. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 1 and 22. Surgery will be performed within 4-6 weeks after completion of preoperative therapy described above. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Preoperative Pembrolizumab With Chemoradiotherapy Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 62 years |
| Body Mass Index (BMI) | 23.20 kg/m^2 |
| Clinical N Stage cN0 | 2 Participants |
| Clinical N Stage cN1 | 5 Participants |
| Clinical N Stage cN2 | 10 Participants |
| Clinical N Stage cN3 | 3 Participants |
| Clinical Stage II | 2 Participants |
| Clinical Stage III | 13 Participants |
| Clinical Stage IVA | 5 Participants |
| Clinical T Stage cT3 | 16 Participants |
| Clinical T Stage cT4a | 4 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 3 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 20 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 19 Participants |
| Smoking History Non-smoker | 6 Participants |
| Smoking History Previous or current smoker | 14 Participants |
| Tumor Length | 6.34 cm |
| Tumor Location Distal third | 4 Participants |
| Tumor Location Middle third | 11 Participants |
| Tumor Location Proximal third | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 13 / 20 |
Outcome results
Primary
Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)
The number of participants with grade 3 and higher-grade treatment-related adverse events. Adverse events were evaluated using CTCAE 4.0, grade 3 treatment-related adverse events and higher-grade adverse events were reported.
Time frame: From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Preoperative Pembrolizumab With Chemoradiotherapy Group | Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events) | 13 Participants |
Secondary
Feasibility (Number of Participants Who Finished Pembrolizumab With Chemoradiotherapy and Receive Surgery Within 4-6 Weeks After Preoperative Therapies)
The number of participants who finished pembrolizumab with chemoradiotherapy and receive surgery within 4-6 weeks after preoperative therapies.
Time frame: From date of treatment allocation until surgery or definitive chemoradiotherapy was applied, whichever came first, assessed up to 5 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Preoperative Pembrolizumab With Chemoradiotherapy Group | Feasibility (Number of Participants Who Finished Pembrolizumab With Chemoradiotherapy and Receive Surgery Within 4-6 Weeks After Preoperative Therapies) | 11 Participants |
Secondary
Pathologic Complete Response
Pathologic complete response was defined as the lack of all signs of cancer in tissue samples removed during surgery after treatment with pembrolizumab and chemoradiotherapy.
Time frame: Two weeks after surgery
Population: Twenty patients were assigned to this group, while, 18 patients received esophagectomy. Two patients did not receive surgery due to the following reasons: one was determined progression disease due to liver metastasis after completion of preoperative therapy; another patient died while awaiting surgery due to severe esophageal hemorrhage.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Preoperative Pembrolizumab With Chemoradiotherapy Group | Pathologic Complete Response | 10 Participants |
Secondary
Radiographic Response
To assess radiographic response to neoadjuvant pembrolizumab with concurrent chemoradiotherapy using RECIST 1.1. Complete metabolic response (cMR), defined as a physiological distribution of FDG uptake on PET-CT with a SUVmax value of less than 4 with no nodal uptake.
Time frame: From date of treatment allocation and during treatment period up to 3 months
Population: Twenty patients were enrolled, and seventeen patients out of them received PET-CT before and after the completion of preoperative treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Preoperative Pembrolizumab With Chemoradiotherapy Group | Radiographic Response | 6 Participants |