Clinical trial NCT04937673: The Neoadjuvant Treatment of Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
Official title: Camrelizumab Combined With Chemotherapy for Neoadjuvant Treatment of Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma：A Phase II Clinical Study to Explore the Relationship Between Biomarkers and Efficacy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Thoracic Esophageal Squamous Cell Carcinoma
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2021-06-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open, two arm phase II clinical study. 40 patients are included in the exploratory study. The dominant population with higher biomarker positive / IO score was identified to provide the basis for the later phase III study. The subjects were randomly divided into the group of camrelizumab combined with paclitaxel and cisplatin or the group of camrelizumab combined with albumin bound paclitaxel and cisplatin according to the ratio of 1:1. The treatment cycle was every 3 weeks. The curative effect was evaluated when the treatment cycle was 2, and the resection of esophageal cancer was considered after 3 cycles. Postoperative adjuvant therapy was based on the patient's condition and surgical results; For patients with R0 resection, postoperative adjuvant treatment is not recommended. For patients with R1 / R2 resection, multi-disciplinary joint discussion and consultation are recommended to propose individualized comprehensive treatment.


Eligibility criteria: Inclusion Criteria:

1. Age: 18-75 years old, male or female;
2. Esophageal squamous cell carcinoma was confirmed by pathology (except for cervical and Suprathoracic tumors that could not be operated);
3. Patients with resectable esophageal squamous cell carcinoma with clinical stage T3-T4a or TxN + M0 (except T4b);
4. ECOG PS score was 0-1;
5. There was at least one measurable lesion (according to recist1.1) or unmeasurable lesion that could be evaluated, and the imaging diagnosis time was ≤ 21 days;
6. The expected survival time was more than 3 months;
7. The function of the main organs was normal, and there were no serious blood, heart, lung, liver, kidney, bone marrow and other functional abnormalities and immunodeficiency diseases. The laboratory examination meets the following requirements:

   1. Hemoglobin (Hb) ≥ 90g / L;
   2. WBC ≥ 3.0 × 109/L； Neutrophil count (NEUT) ≥ 1.5 × 109/L；
   3. Platelet count (PLT) ≥ 100 × 109/L；
   4. Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50 ml / min (Cockcroft Gault formula);
   5. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
   6. The levels of AST and ALT were less than 2.5 times the upper limit of normal (ULN);
8. There was no active bleeding or thrombosis

   1. International normalized ratio INR ≤ 1.5 × ULN；
   2. Partial thromboplastin time APTT ≤ 1.5 × ULN；
   3. Prothrombin time Pt ≤ 1.5ULN;
9. The patients with normal or mild to moderate abnormal lung function (VC% \> 60%, FEV1 \> 1.2L, FEV1% \> 40%, DLco\> 40%) could tolerate esophagectomy;
10. The fertile female subjects were required to conduct blood pregnancy test within 72 hours before the first administration, and the result was negative, and voluntarily used appropriate contraceptive methods during the observation period and within 90 days after the last administration of the study drug; For men, surgical sterilization or consent to appropriate contraceptive methods during the observation period and within 90 days after the last administration of the study drug should be used.
11. The subjects voluntarily joined the study and signed the informed consent form (ICF);
12. The patients with good compliance were expected to follow up the efficacy and adverse events / reactions according to the protocol requirements.

Exclusion Criteria:

1. Subjects who have received or are receiving additional chemotherapy, radiotherapy, targeted or immunotherapy;
2. Any active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy)); The subjects with childhood asthma who had been completely relieved and did not need any intervention or vitiligo in adulthood could be included, but the subjects who needed bronchodilator for medical intervention could not be included;
3. Patients with congenital or acquired immune deficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV DNA ≥ 500 IU / ml), hepatitis C (HCV antibody positive and HCV-RNA higher than the detection limit of the analytical method), or co infection of hepatitis B and hepatitis C;
4. Immunosuppressive drugs were used within 14 days before the first use of the study drug, excluding nasal and inhaled corticosteroids or physiological doses of systemic corticosteroids;
5. Live attenuated vaccine was inoculated within 4 weeks before the first administration or during the study period;
6. Patients with hypertension who can not be reduced to normal range after antihypertensive drug treatment (systolic blood pressure ≤ 140 mmHg / diastolic blood pressure ≤ 90 mmHg);
7. Subjects with uncontrollable clinical cardiac symptoms or diseases, such as (1) heart failure of NYHA II or above (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention;
8. Severe infection (e.g. need for intravenous antibiotics, antifungal or antiviral drugs) occurred within 4 weeks before the first administration, or fever of unknown origin \> 38.5% occurred during the screening period / before the first administration；
9. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation is known;
10. Pregnant or lactating women; The fertile subjects were unwilling or unable to take effective contraceptive measures;
11. Other malignant tumors were found in the past or at the same time, but the cured basal cell carcinoma of skin, carcinoma in situ of cervix and carcinoma in situ of breast were excluded;
12. Known to have allergic history to the drug components of this protocol;
13. Other situations considered unsuitable by the researchers.

Primary outcomes:
measure: biomarkers related to pCR
timeFrame: 9 weeks
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 9 weeks
measure: Disease Control Rate
timeFrame: 9 weeks
measure: Disease free survival
timeFrame: Time from randomization to patient's tumor progression or death
measure: Overall Survival
timeFrame: The time from the beginning of randomization to death due to any cause.
measure: Safety
timeFrame: from first treatment to 90 days after esophagectomy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of GI Oncology, Peking University Cancer Hospital,
state: Beijing
Study officials:
References: