A Study of Simmitinib Plus Irinotecan in Advanced Esophageal Squamous Cell Carcinoma

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: simmitinib plus irinotecan liposome; Drug: irinotecan liposome; Drug: irinotecan

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.

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group Officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Study Locations

• China
  • Harbin
    • Heilongjiang, Harbin, China, 150076
      • Recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Yanqiao Zhang, Ph.D; Phone Number: 0451-86298222; Email: yanqiaozhanggcp@163.com

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 18-70 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: simmitinib plus irinotecan liposome	Drug: simmitinib plus irinotecan liposome; simmitinib plus irinotecan liposome 70 mg/m^2 every 2 weeks
Experimental: irinotecan liposome	Drug: irinotecan liposome; irinotecan liposome 70 mg/m^2 every 2 weeks
Experimental: irinotecan	Drug: irinotecan; irinotecan 180mg/m^2 every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Phase: DLT	Dose Limited Toxicity	From Cycle 1 Day 1 to Cycle 1 Day 28 (each cycle is 28 days)
Dose Escalation Phase: AE	Incidence rate of Adverse Event	From first dose to 30 days post the last dose
Randomized controlled study phase: ORR	Objective Response Rate (ORR) evaluated by investigators based on RECIST 1.1	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	2 years
DCR	Disease Control Rate	2 years
PFS	Progression-free Survival	2 years
DOR	Duration of Objective Response	2 years
Area under plasma concentration (AUC)	Area under the plasma concentration versus time curve (AUC) of simmitinib	2 years
Peak Plasma Concentration (Cmax)	Peak Plasma Concentration (Cmax) of simmitinib	2 years
Time of peak plasma concentration (Tmax)	Time of peak plasma concentration (Tmax) of simmitinib	2 years

Collaborators and Investigators

• Sponsor: Shanghai Runshi Pharmaceutical Technology Co., Ltd
• Investigators: Principal Investigator: Yanqiao Zhang, Ph.D, The Second Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): January 30, 2026

Study Registration Dates

• First Submitted: July 9, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: HA1818-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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