Clinical trial NCT03888092: Z650 in Advanced Esophageal Squamous Cell Carcinoma With EGFR Over Expression or Gene Amplification
Official title: A Phase Ib, Multi-center, Open-label Study of Z650 in Advanced Esophageal Squamous Cell Carcinoma (ECSS) With Epidermal Growth Factor Receptor (EGFR) Over Expression or Gene Amplification
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-03-25
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: It is a multi-center , open-label, singer arm study to explore the safety and efficacy of Z650 in advanced ESCC patients who had experienced systematic chemotherapy. Approximately 45 subjects will be enrolled, each subjects will receive oral Z650, at dose of 350 mg/d, repeatedly until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* History of serious allergic reactions attributed to excipients of Z650, including mannitol, sodium carboxymethyl starch, aerosol, magnesium stearate and silicified microcrystalline cellulose
* Pregnant women, or patients not agree to use of effective contraceptions during the study or within 6 month after the study
* Any other reason the investigator considers the patient is not suitable to participate in the study

Primary outcomes:
measure: Number of patients with adverse events (AEs) as a measure of safety and tolerability
timeFrame: up to 4 weeks after last dose
measure: Number of patients with adverse events (AEs) as a measure of safety and tolerability
timeFrame: up to 4 weeks after last dose
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: up to approximately 24 months
measure: Progression-free Survival (PFS)
timeFrame: up to approximately 24 months
measure: Overall Survival (OS)
timeFrame: up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital, the Fifth Medical Center
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital, the Fifth Medical Center
name: Jianming Xu, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.