Z650 in Advanced Esophageal Squamous Cell Carcinoma With EGFR Over Expression or Gene Amplification

NCT03888092 | Completed Phase 1

• 1 other identifier: PCD-DZ650-17-001
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Z650 in Advanced Esophageal Squamous Cell Carcinoma patients With EGFR Over expression or Gene Amplification.

Conditions

Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of patients with adverse events (AEs) as a measure of safety and tolerability

  AEs assessment via monitoring changes in vital signs (e.g.body temperature, pulse rate, blood pressure, respiratory rate,etc.) and physical examinations(e.g.height, weight, BMI,etc.)

  up to 4 weeks after last dose

• Number of patients with adverse events (AEs) as a measure of safety and tolerability

  AEs assessment via monitoring changes in clinical laboratory parameters (e.g. levels of liver, kidney, and bone marrow function) and ECG (e.g. QTc Interval).

  up to 4 weeks after last dose

Secondary Outcomes (5)

• Overall response rate (ORR)

  up to approximately 24 months

• Disease Control Rate (DCR)

  up to approximately 24 months

• Duration of Response (DOR)

  up to approximately 24 months

• Progression-free Survival (PFS)

  up to approximately 24 months

• Overall Survival (OS)

  up to approximately 24 months

Study Arms (1)

Z650 , Single-arm

EXPERIMENTAL

Z650 will be administered daily, at dose of 350 mg orally

Drug: Z650

Interventions

Z650 DRUG

receive oral Z650 once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days

Also known as: Larotinib

Z650 , Single-arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed Stage IIIB or IV ESCC
• At least experienced one regimens of chemotherapy prior to study
• Histological or cytological evidence of EGFR overexpression or gene copy number increased
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except alopecia)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Life expectancy of ≥ 12 weeks
• Adequate organ function
• Subject Consent
• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to performing this study.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Prior treatments
• EGFR targeted therapy, or major surgery within 4 weeks prior to study treatment
• Nitrosourea and mitomycin chemotherapy within 6 weeks prior to study treatment
• Had received any investigational agent from other clinical study within 4 weeks prior to study treatment or are currently participating in other clinical trials
• Gastrointestinal diseases that could affect the absorption of Z650, (e.g., serious swallowing obstruction, chronic diarrhea, bowel obstruction);
• Symptomatic, untreated or unstable central nervous system metastases (patient are only permitted if treated, asymptomatic and stable for at least 4 weeks prior to start of study treatment)
• History of interstitial lung disease
• Uncontrolled hypertension that require more than two anti-hypertensive agents to control, or systolic blood pressure (BP) \>140mmHg or diastolic BP \>90 mmHg before the first administration
• Doppler ultrasound evaluation of Left ventricular ejection fraction \< 50%
• Male with QTc interval \> 450 ms or female with QTc interval \> 470 ms
• History of immunodeficiency, or other acquired or congenital immunodeficiency, or history of organ transplantation
• Any disease of the following bellowed within 6 months prior to administration:
• Myocardial infarction, or unstable angina, coronary or peripheral artery bypass graft, congestive heart failure, or cerebrovascular events (including transient ischemic attack)
• Active infection of hepatitis B virus (HBV)/hepatitis C virus (HCV), or infection of Human immunodeficiency virus (HIV)
• Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

Chinese PLA General Hospital, the Fifth Medical Center

Beijing, Beijing Municipality, 100071, China

Location

Related Publications (1)

• Liu R, Liu L, Zhao C, Bai Y, Zheng Y, Zhang S, Li N, Yang J, Fan Q, Wang X, Zeng S, Zhang Y, Zhang W, Zhuang Y, Kang N, Jiang Y, Sun H, Xu J. Larotinib in patients with advanced and previously treated esophageal squamous cell carcinoma with epidermal growth factor receptor overexpression or amplification: an open-label, multicenter phase 1b study. BMC Gastroenterol. 2021 Oct 23;21(1):398. doi: 10.1186/s12876-021-01982-4.

  PMID: 34688250 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Jianming Xu, PHD

  Chinese PLA General Hospital, the Fifth Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: March 25, 2019
• Study Start: August 18, 2017
• Primary Completion: December 13, 2022
• Study Completion: December 13, 2022
• Last Updated: March 21, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)