Ignite Creation Date:
2025-12-25 @ 3:52 AM
Ignite Modification Date:
2026-01-12 @ 6:43 PM
Study NCT ID:
NCT06487702
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-05
First Post:
2024-06-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Phase lb/lI Clinical Study in Advanced or Metastatic Esophageal Squamous Cell Carcinoma
Sponsor:
Rui-hua Xu, MD, PhD
Organization:
Study Overview
Official Title:
Fruquintinib Combined With AK104 and Tegafur Gimeracial and Oteracil as Second-ine or After Line Treatment in Advanced or Metastatic ESCC
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a prospective, single-arm, open-label，multi-center, phase Ib/II study, aiming to evaluate the efficacy and safety of Fruquintinib combined With Cadonilimab (AK104) and Tegafur，Gimeracil and Oteracil Potassium in patients with locally advanced or metastatic esophageal squamous cell carcinoma after the failure of first-line treatments.
Detailed Description:
Esophageal cancer is a malignant tumor with high incidence and death rate in the world, especially in china, and Esophageal squamous cell carcinoma (ESCC) is the main pathological type of esophageal carcinoma in China. Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of immunotherapy to chemotherapy, compared with chemotherapy, significantly improved overall survival and progression-free survival in first-line treatments. Treatment of recurrent or metastatic esophageal squamous cell carcinoma is usually poor. New treatments were needed.Fruquintinib is an orally antiangiogenic agents, which target VEGFR1/2/3. Candonilimab (AK104) is a PD-1/CTLA-4 Bispecific Antibody. A combination of Fruquintinib and Candonilimab (AK104) and s-1 for advanced or metastatic esophageal squamous cell carcinoma could be a novel therapy. Therefore, investigators initialize this phase Ib/II study to explore the efficacy and safety of fruquintinib in combination with Candonilimab (AK104) and S-1 treatment in ESCC patients with after failure in 1st-line treatment.
In dose escalation period, 3-12 patients with Esophageal squamous cell carcinoma will be enrolled. Patients meeting enrollment eligibility will receive 21-day cycles of fruquintinib 2-3 mg qd，D1-14,Q3W； combined with Candonilimab 10 mg/kg，D1，Q3W and S-1 (30mg BID for body surface area \<1.25 m2;40mg BID for body surface area ≥1.25 - \<1.5 m2;50mg BID for body surface area ≥1.5m2 ；D1-14,Q3W)
Safety information will be collected till disease progression or intolerable toxicity to determine MTD and/or RPTD of fruquintinib combined with Candonilimab and S-1 in patients with Esophageal squamous cell carcinoma .
This period will include the following 2 dose groups from low to high:
A: Fruquintinib 2 mg qd for 2 weeks followed by 1-week break + Candonilimab 10 mg/kg，intravenous infusion，D1, every 3 weeks+ S-1 ,Calculate dosage based on body surface ,30mg for BSA \<1.25 m2;40 mg for BSA ≥1.25 - \<1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W
B: Fruquintinib 3 mg qd for 2 weeks followed by 1-week break + Candonilimab 10 mg/kg，intravenous infusion，D1, every 3 weeks+ S-1 ,Calculate dosage based on body surface ,30mg for BSA \<1.25 m2;40 mg for BSA ≥1.25 - \<1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W
This study will use traditional 3+3 trial design (3 subjects will be enrolled in each dose group first).
If 1 case of DLT is observed, additional 3 subjects will be enrolled in the same dose group,when no new DLTs occurred, the trial was continued to the next dose level to further evaluate toxicity ,to observe DLT and evaluate MTD.
If there are 2 or more cases of DLT in one dose group, the group lower than this dose group by one level is MTD dose group. If 2 dose group levels MTD was not reached, then the B group dose was RP2D.(DLT was predefined by the investigator in the protocol)
Subjects in the original dose group will continue to receive the next cycle of treatment at the original dose till disease progression or treatment withdrawal due to any of the following reasons: 1) death, 2) intolerable toxicity, 3) pregnancy, 4) the investigator considers the study should be terminated for the subject's best interests, 5) the subject or legal representative requests withdrawal, 6) loss to follow-up, 7) the subject has poor compliance and cannot comply with the study protocol.
In phase II period,patients meeting enrollment eligibility will receive Fruquintinib PR2D in combination with Candonilimab 10 mg/kg，intravenous infusion，D1, every 3 weeks and S-1 ,Calculate dosage based on body surface ,30mg for BSA \<1.25 m2;40 mg for BSA ≥1.25 - \<1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W, till disease progression or treatment withdrawal due to any of the following reasons: 1) death, 2) intolerable toxicity, 3) pregnancy, 4) the investigator considers the study should be terminated for the subject's best interests, 5) the subject or legal representative requests withdrawal, 6) loss to follow-up, 7) the subject has poor compliance and cannot comply with the study protocol.
In dose escalation period, 3-12 patients with Esophageal squamous cell carcinoma will be enrolled. Patients meeting enrollment eligibility will receive 21-day cycles of fruquintinib 2-3 mg qd，D1-14,Q3W； combined with Candonilimab 10 mg/kg，D1，Q3W and S-1 (30mg BID for body surface area \<1.25 m2;40mg BID for body surface area ≥1.25 - \<1.5 m2;50mg BID for body surface area ≥1.5m2 ；D1-14,Q3W)
Safety information will be collected till disease progression or intolerable toxicity to determine MTD and/or RPTD of fruquintinib combined with Candonilimab and S-1 in patients with Esophageal squamous cell carcinoma .
This period will include the following 2 dose groups from low to high:
A: Fruquintinib 2 mg qd for 2 weeks followed by 1-week break + Candonilimab 10 mg/kg，intravenous infusion，D1, every 3 weeks+ S-1 ,Calculate dosage based on body surface ,30mg for BSA \<1.25 m2;40 mg for BSA ≥1.25 - \<1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W
B: Fruquintinib 3 mg qd for 2 weeks followed by 1-week break + Candonilimab 10 mg/kg，intravenous infusion，D1, every 3 weeks+ S-1 ,Calculate dosage based on body surface ,30mg for BSA \<1.25 m2;40 mg for BSA ≥1.25 - \<1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W
This study will use traditional 3+3 trial design (3 subjects will be enrolled in each dose group first).
If 1 case of DLT is observed, additional 3 subjects will be enrolled in the same dose group,when no new DLTs occurred, the trial was continued to the next dose level to further evaluate toxicity ,to observe DLT and evaluate MTD.
If there are 2 or more cases of DLT in one dose group, the group lower than this dose group by one level is MTD dose group. If 2 dose group levels MTD was not reached, then the B group dose was RP2D.(DLT was predefined by the investigator in the protocol)
Subjects in the original dose group will continue to receive the next cycle of treatment at the original dose till disease progression or treatment withdrawal due to any of the following reasons: 1) death, 2) intolerable toxicity, 3) pregnancy, 4) the investigator considers the study should be terminated for the subject's best interests, 5) the subject or legal representative requests withdrawal, 6) loss to follow-up, 7) the subject has poor compliance and cannot comply with the study protocol.
In phase II period,patients meeting enrollment eligibility will receive Fruquintinib PR2D in combination with Candonilimab 10 mg/kg，intravenous infusion，D1, every 3 weeks and S-1 ,Calculate dosage based on body surface ,30mg for BSA \<1.25 m2;40 mg for BSA ≥1.25 - \<1.5 m2; 50mg for BSA ≥1.5m2;BID，D1-14，Q3W, till disease progression or treatment withdrawal due to any of the following reasons: 1) death, 2) intolerable toxicity, 3) pregnancy, 4) the investigator considers the study should be terminated for the subject's best interests, 5) the subject or legal representative requests withdrawal, 6) loss to follow-up, 7) the subject has poor compliance and cannot comply with the study protocol.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: