A Study of Simmitinib Versus Chemotherapy for Participants With Advanced Oesophageal Squamous Cell Carcinoma

Phase 3

Not yet recruiting

Conditions: Advanced Oesophageal Squamous Cell Carcinoma

Interventions: Drug: simmitinib
Drug: investigator's choice of chemotherapy,include docetaxel or irinotecan.

Registration Number: NCT06656091

Lead Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd

Brief Summary: To evaluate the overall survival of simmitinib versus investigator's choice of chemotherapy for Participants with advanced or metastatic oesophageal squamous cell carcinoma who have disease progression after first-line standard therapy.

Detailed Description: This is a randomised, open-label, multicentre, phase 3 study. Participants with advanced or metastatic oesophageal squamous cell carcinoma who have disease progression after first-line standard therapy will be randomly assigned to the experimental group or control group in a 1:1 ratio. The experimental group received treatment with Simmitinib, while the control group received investigator's choice of chemotherapy, include docetaxel or irinotecan.

Recruitment & Eligibility

Status: NOT_YET_RECRUITING

Sex: All

Target Recruitment: 450

Inclusion Criteria

1. Have fully understood and voluntarily sign the ICF for this study; 2. Age of 18-75 years (inclusive), male or female； 3. Histologically or cytologically confirmed esophageal squamous cell carcinoma with locally advanced unresectable, local recurrence or with distant metastasis； 4. Second-line patients with disease progression after only first-line standard therapy（Standard treatment: Chemotherapy with platinum, paclitaxel, or fluorouracil combined with immunosuppressive regimen. Progression during maintenance therapy will be allowed.Concurrent chemoradiotherapy with recurrence or metastasis after surgery is considered as first-line treatment. Progression during Concurrent chemoradiotherapy/ adjuvant/neoadjuvant therapy or within 6 months of the last dose is considered a first-line standard treatment failure）; 5. At least one evaluable lesion according to RECIST 1.1; 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1; 7. Expected survival is more than 3 months； 8. Have recovered from any prior adverse effects of chemotherapy, surgery, radiation, or other antitumor therapy to CTCAE V5.0 criteria ≤ Grade 1 or baseline (except for toxicity such as hair loss that the investigator determines is not a safety risk)； 9. Adequate organ function, defined as:
2. Absolute Neutrophil count (ANC) ≥ 1.5 × 10^9/L;
3. Platelet count (PLT) ≥ 100× 10^9/L;
4. Hemoglobin (Hb) ≥ 90 g/L;
5. Serum creatinine ≤ 1.5 × ULN and Creatinine clearance (CCr)≥60mL/min(According to the Cockcroft-Gault formula);
6. Serum total bilirubin (TBIL) ≤ 1.5 × ULN;
7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5.0 × ULN for patients with liver metastases);
8. Prothrombin time (PT)、activated partial thromboplastin time (APTT)、international normalized ratio(INR)≤1.5 × ULN(No previous anticoagulant therapy) 10. Male and female patients of childbearing age must agree to take effective contraceptive measures during treatment and within 6 months after the last dose of treatment. Female participants must have a negative serum or urine pregnancy test result within 7 days prior to randomization and must be non-lactating.

Exclusion Criteria

1. Patients who have previously received any anti-tumor therapy within 4 weeks prior to randomization; 2. Patients who have previously received major surgical treatment、open biopsy、other clinical trial drug treatment or any live attenuated vaccine within 4 weeks prior to randomization, or are expected to received any live attenuated vaccine during the study.
2. Patients who have previous treatment with anti-angiogenic drugs (such as anlotinib, apatinib, Fruquintinib, Surufatinib, Bevacizumab, etc.) 4. LVEF <50%； 5. BMI≤18.5 kg/m^2； 6. Symptomatic central nervous system (CNS) metastases or meningeal metastases 7. Patients with other types of malignant tumors within 5 years prior to the screening, except for radically resected, non-recurrent skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical cancer in situ, or other carcinoma in situ； 8. Patients with bleeding tendency; active bleeding or a history of heavy bleeding within the past 6 months； 9. Urine protein ≥ ++ and 24 h urine protein > 1.0 g at screening period； 10. Presence of any severe and/or uncontrolled disease before starting treatment； 11. Patients with Liver cirrhosis or active hepatitis； 12. Patients with abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or abdominal abscess within 6 months before randomization； 13. Patient previously had or currently has a mental disorder or suffers from epilepsy and requires treatment； 14. Patients had prior retinal pigment epithelial detachment or have evidence of ongoing retinal pigment epithelial detachment； 15. Any active infection requiring antibiotics or hormones systemic treatment by intravenous infusion within 14 days prior to randomization; 16. Patients had prior interstitial lung disease,or have evidence of active non-infectious pneumonia treated with corticosteroids； 17. Inability to swallow drugs orally, or presence of clinically significant gastrointestinal disorders.

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
simmitinib	simmitinib	simmitinib 6mg,QD ,3 weeks on 1 week off
investigator's choice of chemotherapy	investigator's choice of chemotherapy,include docetaxel or irinotecan.	docetaxel injection 75mg/m\^2,d1,every 3 weeks；or ilinotecan injection 180mg/m\^2,d1,every 2 weeks

Primary Outcome Measures

Name	Time	Method
OS	up to approximately 3 years

Secondary Outcome Measures

Name	Time	Method
ORR	up to approximately 3 years	Objective Response Rate (ORR) evaluated by investigators based on RECIST 1.1
PFS	up to approximately 3 years	Progression-free Survival
DCR	up to approximately 3 years	Disease Control Rate
DOR	up to approximately 3 years	Duration of Objective Response
AE	From first dose to 28 days post the last dose	Incidence rate of Adverse Event
FGF19 protein expression, FGF gene amplification status	baseline	IHC detection of FGF19 protein expression in tumor tissues FISH detection of FGF19 gene amplification status in tumor tissues NGS detection of FGF-FGFR pathway related gene status, including gene amplification, mutation, or fusion
PK	Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle is 28 days)	Plasma Concentration of simmitinib

A Study of Simmitinib Versus Chemotherapy for Participants With Advanced Oesophageal Squamous Cell Carcinoma

Recruitment & Eligibility

Study & Design

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