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

NCT ID: NCT06512428

Last Updated: 2024-07-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-15
• Study Completion Date: 2026-01-30

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.

Conditions

Advanced Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

simmitinib plus irinotecan liposome

Group Type: EXPERIMENTAL

simmitinib plus irinotecan liposome

Intervention Type: DRUG

simmitinib plus irinotecan liposome 70 mg/m\^2 every 2 weeks

irinotecan liposome

Group Type: EXPERIMENTAL

irinotecan liposome

Intervention Type: DRUG

irinotecan liposome 70 mg/m\^2 every 2 weeks

irinotecan

Group Type: EXPERIMENTAL

irinotecan

Intervention Type: DRUG

irinotecan 180mg/m\^2 every 2 weeks

Interventions

simmitinib plus irinotecan liposome

simmitinib plus irinotecan liposome 70 mg/m\^2 every 2 weeks

Intervention Type: DRUG

irinotecan liposome

irinotecan liposome 70 mg/m\^2 every 2 weeks

Intervention Type: DRUG

irinotecan

irinotecan 180mg/m\^2 every 2 weeks

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Runshi Pharmaceutical Technology Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yanqiao Zhang, Ph.D

Role: PRINCIPAL_INVESTIGATOR

The Second Affiliated Hospital of Harbin Medical University

Locations

Harbin Medical University Cancer Hospital

Heilongjiang, Harbin, China

Site Status: RECRUITING

Countries

China

Central Contacts

Clinical Trials Information Group officer

Role: CONTACT

ctr-contact@cspc.cn

86-0311-69085587

Facility Contacts

Yanqiao Zhang, Ph.D

Role: primary

yanqiaozhanggcp@163.com

0451-86298222

Other Identifiers

HA1818-004

Identifier Type: -

Identifier Source: org_study_id