Clinical trial NCT06512428: A Study of Simmitinib Plus Irinotecan in Advanced Esophageal Squamous Cell Carcinoma
Official title: An Open-label, Multicenter Phase II Clinical Trial to Explore the Safety and Efficacy of Simmitinib Plus Irinotecan Liposome in Patients With Advanced Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Esophageal Squamous Cell Carcinoma
Lead sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-07-22
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation Phase:

Dose 1: simmitinib 4mg QD plus irinotecan liposome 70 mg/m\^2 every 2 weeks; Dose 2: simmitinib 6mg 3 weeks on 1 week off plus irinotecan liposome 70 mg/m\^2 every 2 weeks; Dose 3: simmitinib 6mg QD plus irinotecan liposome 70 mg/m\^2 every 2 weeks;

Randomized controlled study Phase:

Randomly assigned to the following 3 groups at 1:1:1 ratio, including simmitinib plus irinotecan liposome, irinotecan liposome, and irinotecan.
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of simmitinib plus irinotecan liposome in the treatment of advanced esophageal squamous cell carcinoma, and to evaluate the PK of the drug and the correlation between biomarkers and clinical efficacy of simmitinib plus irinotecan liposome.

Detailed description: The experiment was divided into two stages. The first stage is dose escalation stage. Rapid titration and "3+3" dose escalation design were used to observe DLT of simmitinib plus irinotecan liposome, and MTD was determined. The second stage is a randomized controlled study. After RP2D was determined in the first stage, participants were randomly assigned to 3 groups in a 1:1:1 ratio, including simmitinib plus irinotecan liposome, irinotecan liposome, and irinotecan.

Eligibility criteria: Inclusion Criteria:

1. Have fully understood and voluntarily sign the ICF for this study;
2. Age of 18-70 years (inclusive), male or female;
3. Esophageal squamous cell carcinoma confirmed histologically or cytologically
4. Second-line patients with disease progression after only first-line standard therapy（Standard treatment: chemotherapy with platinum plus fluorouracil or taxane combined with immunosuppressive regimen .Progression during adjuvant/neoadjuvant therapy or within 6 months of the last dose is considered a first-line standard treatment failure）
5. At least one measurable 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. Adequate organ function, defined as:

   Absolute Neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count (PLT) ≥ 75× 10\^9/L; Hemoglobin (Hb) ≥ 90 g/L; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5.0 × ULN for patients with liver metastases); Serum total bilirubin (TBIL) ≤ 1.5 × ULN; Serum creatinine ≤ 1.5 × ULN and Creatinine clearance (CCr)≥60mL/min; Prothrombin time (PT)、activated partial thromboplastin time (APTT)、international normalized ratio(INR)≤1.5 × ULN;
9. 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.

Exclusion Criteria

1. Patients who have previously received any anti-tumor therapy within 4 weeks prior to the first dose;
2. Patients who have previously received any live attenuated vaccine within 4 weeks before the first use of the study treatment or are expected to received any live attenuated vaccine during the study;
3. Prior systemic treatment with anti-VEGF drugs, irinotecan, or any other topoisomerase I inhibitor
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 \> 1.0g at screening period;
10. Presence of any severe and/or uncontrolled disease before starting treatment;
11. Severe lung disease within 6 months before first dosing ；
12. Any active infection requiring antibiotics or hormones systemic treatment by intravenous infusion within 14 days prior to the first dose;
13. Inability to swallow drugs orally, or presence of clinically significant gastrointestinal disorders

Primary outcomes:
measure: Dose Escalation Phase: DLT
timeFrame: From Cycle 1 Day 1 to Cycle 1 Day 28 (each cycle is 28 days)
measure: Dose Escalation Phase: AE
timeFrame: From first dose to 30 days post the last dose
measure: Randomized controlled study phase: ORR
timeFrame: 2 years
Secondary outcomes:
measure: DCR
timeFrame: 2 years
measure: PFS
timeFrame: 2 years
measure: OS
timeFrame: 2 years
measure: DOR
timeFrame: 2 years
measure: Area under plasma concentration (AUC)
timeFrame: 2 years
measure: Peak Plasma Concentration (Cmax)
timeFrame: 2 years
measure: Time of peak plasma concentration (Tmax)
timeFrame: 2 years
Other outcomes:
Locations:
city: Heilongjiang
country: China
facility: Harbin Medical University Cancer Hospital
state: Harbin
Study officials:
affiliation: The Second Affiliated Hospital of Harbin Medical University
name: Yanqiao Zhang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: