A Study of Adebrelimab Combined With Chemoradiotherapy in the Treatment of Esophageal Small Cell Carcinoma

Phase 2

Not yet recruiting

• Conditions: Esophageal Small Cell Carcinoma
• Interventions: Drug: Etoposide; Drug: Cisplatin; Drug: Carboplatin; Drug: Adebrelimab; Radiation: radiotherapy

• Registration Number: NCT06478264
• Lead Sponsor: Zhangzhou Municipal Hospital

Brief Summary

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

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2024-06
• Study First Submitted: 2024-06-23
• Study First Submitted QC: 2024-06-23
• Last Update Submitted: 2024-06-23
• Study First Posted: 2024-06-27
• Last Update Posted: 2024-06-27
• Study Start: 2024-07-13
• Primary Completion: 2026-07-13
• Study Completion: 2027-07-13

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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:

  8. 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

  9. 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)

  10. 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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single arm	radiotherapy	EP regimen:Etoposide and Cisplatin or Carboplatin Cohort A: Stage I-IVa , EP combined with adebrelimab induction therapy for 2 cycles, sequential thoracic radiotherapy combined with EP chemotherapy for 2 cycles, and adebrelimab immunomaintenance therapy until PD or over 1 year.Thoracic radiotherapy regimen : prescription dose: PTV 50Gy/25f. Cohort B: Stage IVb , EP regimen combined with adebrelimab injection immunotherapy for 4 cycles, PR or SD patients evaluated for 3 months, followed by chest radiotherapy, and adebrelimab immunization continued until PD or full 1 year.Chest radiotherapy : prescribed dose: PTV 30Gy/10f.
Single arm	Etoposide	EP regimen:Etoposide and Cisplatin or Carboplatin Cohort A: Stage I-IVa , EP combined with adebrelimab induction therapy for 2 cycles, sequential thoracic radiotherapy combined with EP chemotherapy for 2 cycles, and adebrelimab immunomaintenance therapy until PD or over 1 year.Thoracic radiotherapy regimen : prescription dose: PTV 50Gy/25f. Cohort B: Stage IVb , EP regimen combined with adebrelimab injection immunotherapy for 4 cycles, PR or SD patients evaluated for 3 months, followed by chest radiotherapy, and adebrelimab immunization continued until PD or full 1 year.Chest radiotherapy : prescribed dose: PTV 30Gy/10f.
Single arm	Cisplatin	EP regimen:Etoposide and Cisplatin or Carboplatin Cohort A: Stage I-IVa , EP combined with adebrelimab induction therapy for 2 cycles, sequential thoracic radiotherapy combined with EP chemotherapy for 2 cycles, and adebrelimab immunomaintenance therapy until PD or over 1 year.Thoracic radiotherapy regimen : prescription dose: PTV 50Gy/25f. Cohort B: Stage IVb , EP regimen combined with adebrelimab injection immunotherapy for 4 cycles, PR or SD patients evaluated for 3 months, followed by chest radiotherapy, and adebrelimab immunization continued until PD or full 1 year.Chest radiotherapy : prescribed dose: PTV 30Gy/10f.
Single arm	Carboplatin	EP regimen:Etoposide and Cisplatin or Carboplatin Cohort A: Stage I-IVa , EP combined with adebrelimab induction therapy for 2 cycles, sequential thoracic radiotherapy combined with EP chemotherapy for 2 cycles, and adebrelimab immunomaintenance therapy until PD or over 1 year.Thoracic radiotherapy regimen : prescription dose: PTV 50Gy/25f. Cohort B: Stage IVb , EP regimen combined with adebrelimab injection immunotherapy for 4 cycles, PR or SD patients evaluated for 3 months, followed by chest radiotherapy, and adebrelimab immunization continued until PD or full 1 year.Chest radiotherapy : prescribed dose: PTV 30Gy/10f.
Single arm	Adebrelimab	EP regimen:Etoposide and Cisplatin or Carboplatin Cohort A: Stage I-IVa , EP combined with adebrelimab induction therapy for 2 cycles, sequential thoracic radiotherapy combined with EP chemotherapy for 2 cycles, and adebrelimab immunomaintenance therapy until PD or over 1 year.Thoracic radiotherapy regimen : prescription dose: PTV 50Gy/25f. Cohort B: Stage IVb , EP regimen combined with adebrelimab injection immunotherapy for 4 cycles, PR or SD patients evaluated for 3 months, followed by chest radiotherapy, and adebrelimab immunization continued until PD or full 1 year.Chest radiotherapy : prescribed dose: PTV 30Gy/10f.

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	1 year	Refers to the proportion of all subjects with a best overall result (BOR) of complete remission (CR) or partial remission (PR) as rated according to RECIST 1.1 criteria. If efficacy of CR or PR is achieved, subjects must be confirmed not less than 4 weeks ± 7 days after the initial evaluation.

Secondary Outcome Measures

Name	Time	Method
Disease control rate (DCR)	1 year	Refers to the proportion of all subjects with a best overall result (BOR) of complete remission (CR), partial remission (PR), and stable disease (SD) as rated according to RECIST 1.1 criteria.
Progression-free survival (PFS)	1 year	PFS was defined as the date from which the subject was first given medication to the date when tumor progression (as assessed by the criteria, with or without continued treatment) was first recorded or the date of death from any cause, whichever came first.
Two-Years Overall Survival Rate	2 years	It refers to the probability that a patient will survive two years after receiving treatment.
AE	1 year	Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated wi...
Overall survival (OS)	2 years	Defined as the time between the date of first dose and the death of the subject due to all causes. Subjects who were alive at the last follow-up visit had OS counted as data censored at the time of the last follow-up visit. The OS of subjects who were lost to follow-up was counted as data censored at the time of last confirmed survival prior to the lost foll...
One-Year Overall Survival Rate	1 year	It refers to the probability that a patient will survive one year after receiving treatment.