REVO: PD-1 Inhibitor Combined With Neoadjuvant Chemotherapy in Subjects With Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Sponsor

Fujian Cancer Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05007145

Collaborator

Suzhou Suncadia Biopharmaceuticals Co., Ltd. (Industry)

Enrollment

Locations

Arms

24.5

Anticipated Duration (Months)

15.3

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to explore the efficacy and safety of compare the efficacy and safety of PD-1 inhibitor and chemotherapy（treatment group） with chemoradiotherapy（control group） in neoadjuvant treatment of resectable thoracic esophageal squamous cell carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Neoplasms Esophageal Squamous Cell Carcinoma	Drug: PD-1 inhibitor Drug: Albumin-Bound Paclitaxel Drug: Cisplatin Radiation: Radiation	Phase 2

Detailed Description

This is a randomized, open-label, phase II study of PD-1 inhibitor combined With neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy in subjects With resectable locally advanced thoracic esophageal squamous cell carcinoma. The patients will be divided into two groups(1:1). In the treatment group, PD-1 inhibitor ,albumin-bound paclitaxel and cisplatin will be given every 3 weeks for 2-4 cycles as neoadjuvant therapy. In the control gourp, albumin-bound paclitaxel and cisplatin will be given every 3 weeks for 2 cycles as neoadjuvant therapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

92 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-label, Phase II Study of PD-1 Inhibitor Combined With Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy in Subjects With Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma

Actual Study Start Date :

Aug 15, 2021

Anticipated Primary Completion Date :

Aug 31, 2023

Anticipated Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD-1 Inhibitor+albumin-bound paclitaxel+cisplatin Participants receive PD-1 Inhibitor 200mg on Day 1 every 3 weeks (Q3W), albumin-bound paclitaxel 125 mg/m^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m^2 on Day 1 Q3W, a total of 2-4 cycles，followed by surgery.	Drug: PD-1 inhibitor PD-1 Inhibitor 200mg D1 Q3W Drug: Albumin-Bound Paclitaxel 125 mg/m^2 D1/D8 Q3W Drug: Cisplatin 75 mg/m^2 D1 Q3W
Active Comparator: Albumin-bound paclitaxel+cisplatin+radiotherapy Participants receive albumin-bound paclitaxel 125 mg/m^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m^2 on Day 1 Q3W, a total of 2 cycles combined with radiotherapy(40Gy/2Gy),followed by surgery.	Drug: Albumin-Bound Paclitaxel 125 mg/m^2 D1/D8 Q3W Drug: Cisplatin 75 mg/m^2 D1 Q3W Radiation: Radiation 40Gy/2.0Gy

Arm

Intervention/Treatment

Experimental: PD-1 Inhibitor+albumin-bound paclitaxel+cisplatin

Participants receive PD-1 Inhibitor 200mg on Day 1 every 3 weeks (Q3W), albumin-bound paclitaxel 125 mg/m^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m^2 on Day 1 Q3W, a total of 2-4 cycles，followed by surgery.

Drug: PD-1 inhibitor

PD-1 Inhibitor 200mg D1 Q3W

Drug: Albumin-Bound Paclitaxel

125 mg/m^2 D1/D8 Q3W

Drug: Cisplatin

75 mg/m^2 D1 Q3W

Active Comparator: Albumin-bound paclitaxel+cisplatin+radiotherapy

Participants receive albumin-bound paclitaxel 125 mg/m^2 on Day 1, 8 Q3W, and cisplatin 75 mg/m^2 on Day 1 Q3W, a total of 2 cycles combined with radiotherapy(40Gy/2Gy),followed by surgery.

Drug: Albumin-Bound Paclitaxel

125 mg/m^2 D1/D8 Q3W

Drug: Cisplatin

75 mg/m^2 D1 Q3W

Radiation: Radiation

40Gy/2.0Gy

Outcome Measures

Primary Outcome Measures

Pathologic complete response (pCR) rate [Within 14 working days after surgery]

Secondary Outcome Measures

R0 resection rate [Within 14 working days after surgery]
Overall Survival (OS) [Up to 8 years]
OS is defined as the time from randomization until death from any cause.
Disease Free Survival (DFS) [Up to 8 years]
The time from the first day of the date of surgery to local or distant recurrence, or death caused by any cause, whichever occurs first;

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Volunteered to participate in the study, signed the informed consent form;
Histologically or cytological confirmed esophageal squamous cell carcinoma;
Patients with resectable disease of primary tumor in thoracic esophagus (cT1b-4aN1-3M0, cT3-4aN0M0) evaluated by CT/MRI/EUS;
Expected R0 resection;
Aged 18-75 years, male or female;
ECOG PS 0-1;
Without prior treatments including surgery, chemotherapy, radiotherapy, and targeting treatment for esophageal cancer;
Surgery is planned after neoadjuvant treatment;
Without any contraindication of operation;
Adequate organ function as follows: 1) Routine blood test: Leukocytes >=3.0x10^{9/L;
Absolute neutrophil count >=1.0x10}9/L; Platelet >=80x10^9/L; Hemoglobin >=90 g/L; 2) Blood biochemical test: Total bilirubin <=1.5 ULN; ALT <=2.5 ULN; AST <=2.5 ULN; Serum creatinine <=1.5 ULN or creatinine clearance rate >=50 mL/min (Cocheroft-Gault); 3) Coagulation function test: INR <=1.5 ULN; APTT <=1.5 ULN;
For females of child bearing potential, a negative serum/urine pregnancy test result within 72h before study treatment. For female and male participants of reproductive potential must be willing to use adequate contraception for the course of the study until 3 months after the last dose of any of the drugs in the study;
Had good compliance and cooperated with the follow-up.

Exclusion Criteria:

The tumor invades the adjacent organs of the esophageal lesion (aorta or trachea);
Patients with supraclavicular lymph node metastasis;
Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage;
Poor nutritional status, BMI < 18.5 Kg/m2; If corrected after nutritional support before randomization, enrollment can be further considered after evaluation by the principal investigator;
Has a history of allergy to monoclonal antibody, any component of PD-1 Inhibitor, paclitaxel, cisplatin or other platinum drugs;
Has received or is receiving any of the following treatments: A)any anti-tumor radiation, chemotherapy or other treatment drugs; B) Immunosuppressive drugs or whole-body hormone drugs are being used for immunosuppressive purposes within 2 weeks prior to the first use of the study drug (dose > 10mg/ day prednisone or equivalent dose);Inhalation or topical use of steroids and 10 mg/ day prednisone or equivalent dose of adrenocortical hormone replacement is permitted in the absence of active autoimmune disease; C) Received attenuated vaccine within 4 weeks before the first use of the study drug; D) Major surgery or severe trauma within 4 weeks prior to the first use of the study drug;
History of any active autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypohysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy);Patients with psoriasis or childhood asthma/allergy who have been in complete remission and do not need any intervention as adults may be considered for inclusion, but patients requiring medical intervention with bronchodilators may not be included;
History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, or history of organ transplantation or allogeneic bone marrow transplantation;
Present of poorly controlled cardiac symptoms or disease, including but not limited to: (1) heart failure with NYHA class II or above (2) unstable angina, （3）myocardial infarction occurred within 1 year (4) clinical significance supraventricular or ventricular arrhythmias without clinical intervention or poorly controlled after clinical intervention;
Severe infection (CTCAE > 2) occurred within 4 weeks prior to the first use of the study drug, such as severe pneumonia, bacteremia, infection complications requiring hospitalization, etc.;Baseline chest imaging indicated active pulmonary inflammation, infection signs and symptoms within 14 days prior to the first use of the study drug, or the need for oral or intravenous antibiotic treatment, except prophylactic antibiotic usage;
Patients who are found to have active pulmonary tuberculosis infection through medical history or CT, or have active pulmonary tuberculosis infection history within 1 year before enrollment, or have active pulmonary tuberculosis infection history more than 1 year before but without regular treatment;
Have hereditary bleeding tendency or coagulation dysfunction. There were clinically significant bleeding symptoms or a clear bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood++ and above at baseline;
Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10^4 copies/mL), hepatitis C (HCV antibody positive, and HCV RNA higher than the detection limit of analytical method);
Other malignancies diagnosed within 5 years prior to the first use of the study drug, except those with a low risk of metastasis or death (5-year survival rate > 90%), such as adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix;
Pregnant or lactating women;
In the investigator's judgment, there were other factors that might have contributed to the forced termination of the study, such as the need for combined treatment with other serious medical conditions (including mental illness), alcohol and drug abuse, family or social factors that might have affected the safety or compliance of the subjects.

Contacts and Locations

Locations

	Site	City	State	Country
1	Fujian Cancer Hospital	Fuzhou	Fujian	China
2	the Second Hospital of Longyan	Longyan	Fujian	China
3	the First Hospital of Putian City	Putian	Fujian	China
4	Fujian Medical University 2nd Affiliated Hospital	Quanzhou	Fujian	China
5	Quanzhou First Hospital	Quanzhou	Fujian	China
6	the First Affiliated Hospital of Xiamen University	Xiamen	Fujian	China