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

Official title

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

Overview

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.

Interventions

• Drug simmitinib
  simmitinib 6mg,QD ,3 weeks on 1 week off
• 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

Primary outcome measures

• OS [Time frame: up to approximately 3 years]

Secondary outcome measures (7)

• ORR [Time frame: up to approximately 3 years]
• PFS [Time frame: up to approximately 3 years]
• DCR [Time frame: up to approximately 3 years]
• DOR [Time frame: up to approximately 3 years]
• AE [Time frame: From first dose to 28 days post the last dose]
• FGF19 protein expression, FGF gene amplification status [Time frame: baseline]
• PK [Time frame: Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle is 28 days)]

Eligibility criteria

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:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06656091 · HA1818-008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗