Clinical trial NCT06478264: A Study of Adebrelimab Combined With Chemoradiotherapy in the Treatment of Esophageal Small Cell Carcinoma
Official title: Efficacy and Safety of Adebrelimab Combined With Chemoradiotherapy in the Treatment of Esophageal Small Cell Carcinoma: a Single-arm, Multicenter, Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Esophageal Small Cell Carcinoma
Keywords: Esophageal Small Cell Carcinoma
Adebrelimab
chemoradiotherapy
Lead sponsor: Zhangzhou Municipal Hospital
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of adebrelimab combined with chemoradiotherapy in the treatment of esophageal small cell carcinoma


Eligibility criteria: Inclusion Criteria:

* 1. Sign a written informed consent to join the study voluntarily;
* 2. Histologically or cytologically confirmed patients with small cell carcinoma of the esophagus staging T1N0M0 but unable to tolerate surgery or refusing surgery and patients staging T2-4N0-3M0 \[according to AJCC 8th edition TNM criteria\];
* 3. Age 18-75 years old, male or female;
* 4. ECOG PS 0-1;
* 5. No previous systemic treatment for esophageal small cell carcinoma;
* 6. At least one measurable lesion (according to RECIST1.1 criteria);
* 7. Normal functioning of major organs, including:

  1. Blood routine examination (no blood component, cell growth factor, white enhancer, platelet enhancer, anemia correction drugs are allowed within 14 days before the first use of the study drug) :

     White blood cell count ≥4.0×10\^9/L

     Neutrophil count ≥1.5×10\^9/L

     Platelet count ≥80×10\^9/L

     Hemoglobin ≥90 g/L
  2. Blood biochemical examination:

     Total bilirubin ≤1.5×ULN

     ALT≤2.5 x ULN, AST≤2.5 x ULN,

     Serum creatinine ≤1.5×ULN, or creatinine clearance ≥50mL/min (Cocheroft-Gault formula, see Annex 2)
  3. Coagulation function:

International Standardized ratio (INR) ≤1.5×ULN

Activated partial thromboplastin time (APTT) ≤1.5×ULN

* 8. Patients must submit pre-treatment tumor tissue samples during the study period;
* 9. Expected survival ≥12 weeks;
* 10. Fertile female subjects are required to take a serum or urine pregnancy test with a negative result within 72 hours before starting the study drug administration, and to use effective contraception (such as an IUD, contraceptive pill or condom) during the trial period and for at least 3 months after the last drug administration; For male subjects whose partners are women of reproductive age, effective contraception should be used during the trial period and within 3 months after the last dose;
* 11. The subjects had good compliance and cooperated with follow-up visits.

Exclusion Criteria:

* 1. Esophageal perforation or hematemesis;
* 2. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage;
* 3. Uncontrolled hypercalcemia or symptomatic hypercalcemia;
* 4. Other malignancies diagnosed within 5 years prior to the first use of the investigational drug, except malignancies with a low risk of metastasis or death (5-year survival \> 90%), such as adequately treated skin basal cell carcinoma or squamous cell skin cancer or cervical carcinoma in situ, may be considered for inclusion;
* 5. History of any active autoimmune disease or autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (may be considered after hormone replacement therapy); Patients with psoriasis or childhood asthma/allergies in complete remission without any intervention as adults may be considered for inclusion, but patients requiring medical intervention with bronchodilators may not be included;
* 6. Previously received immune checkpoint blocking therapy;
* 7. Subjects who required systemic corticosteroids (\> 10 mg/ day effective dose of prednisone) or other immunosuppressive agents within 14 days prior to initial dosing or during the study period. However, in the absence of active autoimmune disease, subjects were allowed to use topical or inhaled steroids and adrenal hormone replacement therapy at a dose ≤10 mg/ day of prednisone effectiveness.
* 8. There are clinical symptoms or diseases of heart that are not well controlled, including but not limited to: (1) NYHA grade II or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, (4) Clinically significant supraventricular or ventricular arrhythmias that are not well controlled without or after clinical intervention;
* 9. Poor nutritional status, BMI \< 18.5 Kg/m\^2; If it is corrected before enrollment after symptomatic nutritional support, it can continue to be considered for enrollment after evaluation by the principal investigator;
* 10. Adverse events greater than grade 2 caused by treatment received before the first use of the investigatory drug that have not recovered (i.e., become grade 1 or reach baseline level), and adverse events (such as neurotoxicity) that are difficult to recover quickly as determined by the investigator can be included;
* 11. History of allergy to any component of adbelimab, etoposide, cisplatin or carboplatin;
* 12. A history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation;
* 13. Severe infections (CTCAE \> Grade 2), such as severe pneumonia requiring hospitalization, bacteremia, and infection complications, occurred within 4 weeks prior to the first use of the study drug; Baseline chest imaging indicated active pulmonary inflammation, signs and symptoms of infection within 14 days prior to the first use of the study drug, or the need for oral or intravenous antibiotic treatment, except in cases of prophylactic antibiotic use;
* 14. Patients found to have active pulmonary tuberculosis infection through medical history or CT examination, or had a history of active pulmonary tuberculosis infection within 1 year before enrollment, or had a history of active pulmonary tuberculosis infection more than 1 year ago without formal treatment;
* 15. Hereditary bleeding tendency or blood clotting dysfunction. There were clinically significant bleeding symptoms or definite bleeding tendencies within 3 months prior to enrollment, such as hemorrhagic gastric ulcer, stool occult blood ++ or above at baseline;
* 16. Active hepatitis B (HBV DNA≥2000 IU/mL or 10\^4 copies/mL), hepatitis C (hepatitis C antibody positive and HCV RNA higher than the lower limit of assay);
* 17. Pregnant or lactating women;
* 18. The investigator determined that there were other factors that might have led to the forced termination of the study, such as other serious medical conditions (including mental illness) requiring co-treatment, alcohol, substance abuse, family or social factors, and factors that might have affected the safety or adherence of the subjects.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 1 year
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: 1 year
measure: Progression-free survival (PFS)
timeFrame: 1 year
measure: Overall survival (OS)
timeFrame: 2 years
measure: One-Year Overall Survival Rate
timeFrame: 1 year
measure: Two-Years Overall Survival Rate
timeFrame: 2 years
measure: AE
timeFrame: 1 year
Other outcomes:
measure: Explore potential biomarkers in tumor tissue
timeFrame: 1 year
measure: Explore potential biomarkers in the Peripheral Blood of Cancer Patients
timeFrame: 1 year
Locations:
Study officials:
affiliation: Zhangzhou Municipal Hospital
name: Weilin Chen
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Xiamen University
name: Yiming Li
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Xiamen University
name: Chong Deng
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhongshan Hospital Affiliated to Xiamen University
name: Shouguo Li
role: PRINCIPAL_INVESTIGATOR
affiliation: Xiamen Second Hospital
name: Yuyi Lin
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of Fujian Medical University
name: Qunrong Cai
role: PRINCIPAL_INVESTIGATOR
affiliation: Quanzhou First Hospital
name: Wenjie Cai
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wen J, Fang S, Hu Y, Xi M, Weng Z, Pan C, Luo K, Ling Y, Lai R, Xie X, Lin X, Lin T, Chen J, Liu Q, Fu J, Yang H. Impacts of neoadjuvant chemoradiotherapy on the immune landscape of esophageal squamous cell carcinoma. EBioMedicine. 2022 Dec;86:104371. doi: 10.1016/j.ebiom.2022.104371. Epub 2022 Nov 23.