Trial Title:
Combination Immunotherapy of Adebrelimab With Apatinib and Tegafur for Immune Rechallenge Therapy in Esophageal Squamous Cell Carcinoma
NCT ID:
NCT06339619
Condition:
Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Apatinib
Tegafur
Conditions: Keywords:
immunotherapy rechallenge
ESCC
Adebrelimab
Apatinib
PD-1 inhibitors
Tegafur
First-line treatment failure
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Adebrelimab
Description:
20mg/kg ivgtt D1 Q3W
Arm group label:
Adebrelimab+Apatinib+Tegafur
Intervention type:
Drug
Intervention name:
Apatinib
Description:
250mg PO QD
Arm group label:
Adebrelimab+Apatinib+Tegafur
Intervention type:
Drug
Intervention name:
Tegafur
Description:
dosing based on body surface area：BSA<1.25m2,40mg; BSA=1.25～1.5m2,50mg; BSA>1.5m2,
60mg，PO QD D1-21 Q3W
Arm group label:
Adebrelimab+Apatinib+Tegafur
Summary:
The goal of this single-arm study is to explore the efficacy and safety of Adebrelimab in
combination with Apatinib and Tegafur for the treatment of locally advanced or metastatic
esophageal squamous cell carcinoma that has failed first-line standard treatment with
PD-1 inhibitors in combination with chemotherapy.
Detailed description:
Background: Although immune combined chemotherapy has established its position as the
first-line standard treatment for locally advanced unresectable or metastatic esophageal
cancer, resistance and disease progression inevitably occur in most patients. While
earlier studies have shown some therapeutic advantages of the combination of PD-1/PDL1
inhibitors with anti-angiogenic drugs, the efficacy as a second-line treatment remains
unsatisfactory, necessitating further exploration of combination therapies such as
chemotherapy.We conduct this single-arm study is to explore the efficacy and safety of
Adebrelimab in combination with Apatinib and Tegafur in treating the patients with
locally advanced or metastatic esophageal squamous cell carcinoma who has failed
first-line standard treatment with PD-1 inhibitors in combination with chemotherapy.
Method: This is a prospective single arm two-stage phase II study, with an intended
enrollment of 32 patients. Eligible patients with esophageal squamous cell carcinoma will
receive Adebrelimab at a dose of 20mg/kg, on day 1 via intravenous drip every 21 days, in
combination with Apatinib at a dose of 250mg orally once daily on days 1-21 every 21
days, and Tegafur orally once daily on days 1-21 every 21 days（BSA<1.25m2,40mg;
BSA=1.25～1.5m2,50mg;BSA>1.5m2, 60mg）. Each treatment cycle lasts for 21 days. Treatment
will continue until disease progression, intolerable toxicity, withdrawal of informed
consent, or death. Imaging evaluation for efficacy will be conducted every 6 to 8 weeks
(±7 days) after the start of the initial treatment until disease progression, death,
initiation of new anticancer therapy, withdrawal of informed consent, loss to follow-up,
or study termination. The primary endpoint is objective response rate (ORR), and
secondary endpoints include progression-free survival (PFS), overall survival (OS),
disease control rate (DCR), and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 18-75 years old, both sexes.
2. Esophageal squamous cell carcinoma confirmed by histology or cytology with locally
advanced unresectable or distant metastasis (according to AJCC 8th edition).
3. ECOG PS score of 0 ~ 1.
4. Expected survival ≥3 months.
5. Patients who have failed first-line immunotherapy combined with chemotherapy.
6. At least one measurable or unmeasurable lesion according to RECIST V1.1 criteria
(subjects with intracranial lesions alone were excluded from this study).
7. Ability to swallow investigational drugs .
8. The functional level of the organ must meet the following requirements. (1)
ANC≥1.5×109/L; (2) PLT≥100×109/L; (3) Hb≥90 g/L; (4) Serum albumin ≥30 g/L; (5)
TBIL≤1.5×ULN; ALT and AST≤2.5 x ULN; For patients with liver metastases, ALT and
AST≤5×ULN; (6) Cr ≤1.5×ULN, or creatinine clearance ≥50mL/min as calculated by the
Cockcroft-Gault formula; (7) Patients with urinary protein ≥++ should undergo
further 24-hour quantitative detection of urinary protein, and the detection result
should be<1.0g.
9. Within 7 days prior to enrollment, women of reproductive age must confirm a negative
serum pregnancy test and consent to use effective contraception during the study
drug use period and within 2 months after the last dose.
10. Subjects voluntarily participate in the study after fully informed consent and sign
the informed consent.
Exclusion Criteria:
1. Have been diagnosed with other malignancies within 5 years, excluding: curable
carcinoma in situ of the cervix, skin basal cell carcinoma or squamous cell
carcinoma, or any other tumor that has been cured .
2. Patients who had previously received treament of Adebrelimab, Apatinib or Tegafur.
3. The following conditions occurred in the previous treatment history. (1)Used Chinese
medicine anti-tumor treatment within 2 weeks; (2)Received other anti-tumor therapy
within 4 weeks, including but not limited to chemotherapy, radiotherapy, and
targeted therapy.
4. Have not recovered from adverse events caused by prior antitumor therapy (i.e., ≤
grade 1 or at baseline).
5. Subjects who have participated in or are participating in other clinical trials
within 4 weeks.
6. Received major surgery within 4 weeks or anticipated to undergo major surgery during
the study period.
7. Subject is currently using a CYP3A strong inhibitor or inducer, or has discontinued
a strong inhibitor for less than 5 half-lives of the medication or discontinued a
strong inducer for less than 5 half-lives of the medication or 14 days (whichever is
longer) before dosing.
8. Current need for treatment of central nervous system metastases or uncontrolled
central nervous system metastases.
9. Risk of severe bleeding or esophageal fistula.
10. Clinically significant gastrointestinal abnormalities that may affect the intake,
transport, or absorption of the drug.
11. Those with active gastrointestinal ulcers, active gastrointestinal bleeding, or
perforation.
12. Within the 12 months prior to enrollment, individuals with any of the following
conditions: myocardial infarction, coronary artery bypass grafting or peripheral
artery bypass grafting surgery, congestive heart failure (III-IV graded by New York
Heart Association), etc.; unstable angina within the 6 months prior to enrollment.
13. Within the 12 months prior to enrollment, occurrence of thrombotic events or embolic
events, such as cerebrovascular accidents (including transient ischemic attacks),
deep vein thrombosis, pulmonary embolism, etc., or patients currently receiving
thrombolytic or anticoagulant therapy such as warfarin, heparin, or other similar
medications.
14. Fridericia-corrected QT interval (QTcF)>470 ms; history of congenital long QT
syndrome; history of any clinically significant ventricular arrhythmias (such as
ventricular tachycardia, ventricular fibrillation, or torsades de pointes); left
ventricular ejection fraction (LVEF) <50%.
15. Those with uncontrollable pleural effusion, pericardial effusion, pelvic effusion,
or ascites requiring repeated drainage.
16. Past or current interstitial lung disease or immune-related pneumonia; currently
suffering from drug-induced pneumonia, radiation pneumonia requiring steroid
therapy, or clinically symptomatic active pneumonia, or other moderate to severe
pulmonary diseases severely affecting lung function.
17. Active infection during screening, or unexplained fever>38.5°C within 2 weeks prior
to randomization.
18. Active hepatitis B or hepatitis C.
19. Received live vaccines within 4 weeks prior toenrollment and/or planned to receive
live vaccines after enrollment.
20. Those with congenital or acquired immunodeficiency (such as HIV-infected
individuals).
21. History of organ transplantation or allogeneic bone marrow transplantation.
22. Individuals deemed by the investigator to have other serious acute or chronic
illnesses unsuitable for participation in the clinical trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Address:
City:
Guangzhou
Zip:
510030
Country:
China
Status:
Recruiting
Contact:
Last name:
Minghui Wang, Dr.
Phone:
13826276828
Email:
wmingh@mail.sysu.edu.cn
Investigator:
Last name:
Minghui Wang, Dr.
Email:
Principal Investigator
Start date:
March 11, 2024
Completion date:
September 1, 2026
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06339619
