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

NCT ID: NCT06478264

Last Updated: 2024-06-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-13
• Study Completion Date: 2027-07-13

Brief Summary

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

Conditions

Esophageal Small Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm

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.

Group Type: EXPERIMENTAL

Etoposide

Intervention Type: DRUG

100mg/m\^2, intravenous infusion for 1-3 days,21 days/cycle, 4 cycles

Cisplatin

Intervention Type: DRUG

25mg/m\^2 ,intravenous infusion for 1-3 days ,21 days/cycle, 4 cycles

Carboplatin

Intervention Type: DRUG

Carboplatin (AUC = 5) on 1 Day,21 days/cycle, 4 cycles ;

Adebrelimab

Intervention Type: DRUG

1200mg adebrelimab was given intravenously on 2 day after chemotherapy,21 days/cycle, continuous use.

radiotherapy

Intervention Type: RADIATION

Stage I-IVa , prescription dose: PTV 50Gy/25f. Stage IVb ,prescribed dose: PTV 30Gy/10f.

Interventions

Etoposide

100mg/m\^2, intravenous infusion for 1-3 days,21 days/cycle, 4 cycles

Intervention Type: DRUG

Cisplatin

25mg/m\^2 ,intravenous infusion for 1-3 days ,21 days/cycle, 4 cycles

Intervention Type: DRUG

Carboplatin

Carboplatin (AUC = 5) on 1 Day,21 days/cycle, 4 cycles ;

Intervention Type: DRUG

Adebrelimab

1200mg adebrelimab was given intravenously on 2 day after chemotherapy,21 days/cycle, continuous use.

Intervention Type: DRUG

radiotherapy

Stage I-IVa , prescription dose: PTV 50Gy/25f. Stage IVb ,prescribed dose: PTV 30Gy/10f.

Intervention Type: RADIATION

Other Intervention Names

SHR-1316

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhangzhou Municipal Hospital

OTHER

Sponsor Role: lead

Responsible Party

Weilin Chen

Head of radiation oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weilin Chen

Role: PRINCIPAL_INVESTIGATOR

Zhangzhou Municipal Hospital

Yiming Li

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Xiamen University

Chong Deng

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Xiamen University

Shouguo Li

Role: PRINCIPAL_INVESTIGATOR

Zhongshan Hospital Affiliated to Xiamen University

Yuyi Lin

Role: PRINCIPAL_INVESTIGATOR

Xiamen Second Hospital

Qunrong Cai

Role: PRINCIPAL_INVESTIGATOR

The Second Affiliated Hospital of Fujian Medical University

Wenjie Cai

Role: PRINCIPAL_INVESTIGATOR

Quanzhou First Hospital

Central Contacts

Weilin Chen

Role: CONTACT

cwlqiao@163.com

13709385466

References

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.

Reference Type: RESULT

PMID: 36434949 (View on PubMed)

Other Identifiers

ADVENT-ESCC

Identifier Type: -

Identifier Source: org_study_id