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

Simmitinib Versus Investigator's Choice of Chemotherapy for Participants With Advanced or Metastatic Oesophageal Squamous Cell Carcinoma : a Randomised, Open-label, Multicentre, Phase 3 Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Oesophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: simmitinib; Drug: investigator's choice of chemotherapy,include docetaxel or irinotecan.

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.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 031169085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

  1. Absolute Neutrophil count (ANC) ≥ 1.5 × 10^9/L;
  2. Platelet count (PLT) ≥ 100× 10^9/L;
  3. Hemoglobin (Hb) ≥ 90 g/L;
  4. Serum creatinine ≤ 1.5 × ULN and Creatinine clearance (CCr)≥60mL/min(According to the Cockcroft-Gault formula);
  5. Serum total bilirubin (TBIL) ≤ 1.5 × ULN;
  6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5.0 × ULN for patients with liver metastases);
  7. 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.

  3. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: simmitinib; simmitinib 6mg,QD ,3 weeks on 1 week off	Drug: simmitinib; simmitinib 6mg,QD ,3 weeks on 1 week off
Active Comparator: investigator's choice of chemotherapy; docetaxel injection 75mg/m^2,d1,every 3 weeks；or ilinotecan injection 180mg/m^2,d1,every 2 weeks	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
OS	up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate (ORR) evaluated by investigators based on RECIST 1.1	up to approximately 3 years
PFS	Progression-free Survival	up to approximately 3 years
DCR	Disease Control Rate	up to approximately 3 years
DOR	Duration of Objective Response	up to approximately 3 years
AE	Incidence rate of Adverse Event	From first dose to 28 days post the last dose
FGF19 protein expression, FGF gene amplification status	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	baseline
PK	Plasma Concentration of simmitinib	Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd
• Investigators: Principal Investigator: Ruihua Xu, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): October 31, 2024
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: October 14, 2024
• First Submitted That Met QC Criteria: October 23, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Docetaxel; Irinotecan
• Other Study ID Numbers: HA1818-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No