Trial Outcomes & Findings for Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus (NCT NCT03792347)

Last Updated: 2023-11-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose

Results posted on

2023-11-22

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Preoperative Pembrolizumab With Chemoradiotherapy Group n=20 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	20 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment China	20 Participants n=5 Participants
Body Mass Index (BMI)	23.20 kg/m^2 n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	3 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	17 Participants n=5 Participants
Smoking History Non-smoker	6 Participants n=5 Participants
Smoking History Previous or current smoker	14 Participants n=5 Participants
Tumor Length	6.34 cm n=5 Participants
Tumor Location Proximal third	5 Participants n=5 Participants
Tumor Location Middle third	11 Participants n=5 Participants
Tumor Location Distal third	4 Participants n=5 Participants
Clinical T Stage cT3	16 Participants n=5 Participants
Clinical T Stage cT4a	4 Participants n=5 Participants
Clinical N Stage cN0	2 Participants n=5 Participants
Clinical N Stage cN1	5 Participants n=5 Participants
Clinical N Stage cN2	10 Participants n=5 Participants
Clinical N Stage cN3	3 Participants n=5 Participants
Clinical Stage II	2 Participants n=5 Participants
Clinical Stage III	13 Participants n=5 Participants
Clinical Stage IVA	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose

Outcome measures

Outcome measures
Measure	Preoperative Pembrolizumab With Chemoradiotherapy Group n=20 Participants 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.
Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)	13 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Preoperative Pembrolizumab With Chemoradiotherapy Group n=20 Participants 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.
Feasibility (Number of Participants Who Finished Pembrolizumab With Chemoradiotherapy and Receive Surgery Within 4-6 Weeks After Preoperative Therapies)	11 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Preoperative Pembrolizumab With Chemoradiotherapy Group n=18 Participants 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.
Pathologic Complete Response	10 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Preoperative Pembrolizumab With Chemoradiotherapy Group n=17 Participants 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.
Radiographic Response	6 Participants

Adverse Events

Preoperative Pembrolizumab With Chemoradiotherapy Group

Serious events: 13 serious events

Other events: 20 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Preoperative Pembrolizumab With Chemoradiotherapy Group n=20 participants at risk 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.
Blood and lymphatic system disorders Leukopenia	10.0% 2/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Blood and lymphatic system disorders Decreased neutrophil count	5.0% 1/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Blood and lymphatic system disorders Lymphopenia	60.0% 12/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Esophageal hemorrhage	5.0% 1/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.

Other adverse events

Other adverse events
Measure	Preoperative Pembrolizumab With Chemoradiotherapy Group n=20 participants at risk 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.
Blood and lymphatic system disorders Leukopenia	90.0% 18/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Blood and lymphatic system disorders Decreased neutrophil count	40.0% 8/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Blood and lymphatic system disorders Lymphopenia	40.0% 8/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Blood and lymphatic system disorders Anemia	80.0% 16/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	20.0% 4/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
General disorders Alopecia	55.0% 11/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
General disorders Anorexia	45.0% 9/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Constipation	20.0% 4/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Diarrhea	10.0% 2/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
General disorders Fatigue	55.0% 11/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Nausea	40.0% 8/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Vomiting	15.0% 3/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Esophagitis	55.0% 11/20 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Respiratory, thoracic and mediastinal disorders Postoperative Pneumonia	22.2% 4/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Respiratory, thoracic and mediastinal disorders Atelectasis	22.2% 4/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Respiratory, thoracic and mediastinal disorders Pleural effusion	16.7% 3/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Respiratory, thoracic and mediastinal disorders Pneumothorax	5.6% 1/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Respiratory, thoracic and mediastinal disorders Anastomotic leakage	5.6% 1/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Gastrointestinal fistula	5.6% 1/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Skin and subcutaneous tissue disorders Wound infection	5.6% 1/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Injury, poisoning and procedural complications Hoarseness	22.2% 4/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Gastrointestinal disorders Dysphagia	5.6% 1/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.
Respiratory, thoracic and mediastinal disorders Postoperative intrathoracic hemorrhage	5.6% 1/18 • From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) 4.0.

Additional Information

Prof. Hecheng Li, Chair of Thoracic Surgery

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Phone: (86)13917113402

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place