A Study of Donafenib Monotherapy in Advanced Oesophageal Cancer

Study Overview
=================
Brief Summary
-----------------
This open-label, one-center, noncomparative, two-stages phase 1B trial assessed the tyrosine kinase inhibitor donafenib tosylate tablets(400 mg/d,200mg bid) in patients with advanced, inoperable oesophageal cancer progressing after chemotherapy . The primary endpoint is the safety.The secondary endpoints are tumor response and progression-free survival.

Detailed Description
-----------------
This open-label, noncomparative, two-part phase 1B trial recruited patients with advanced, inoperable oesophageal cancer. The primary objectives were to assess the safety for donafenib tosylate tablets .The secondary objectives were to estimate tumor response, progression-free survival, duration of response, and disease control rate (response plus stable disease); to evaluate changes in quality of life(QoL); This study is 2-stages designing. The investigators plan to enroll 19 patients in the first stage study. The investigators will start the secondary stage study if the disease control rate >=8/19.

Official Title
-----------------
A Phase 1B Study of Donafenib Monotherapy in Advanced Oesophageal Cancer Progressing After Chemotherapy

Conditions
-----------------
Oesophageal Cancer

Intervention / Treatment
-----------------
* Drug: donafenib tosilate tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients provided written, informed consent. Have histologically confirmed advanced oesophageal squamous-cell carcinoma, or type I/II Siewert junctional tumours. Have received up to two previous chemotherapy regimens( Platinum containing regimens & Paclitaxel / docetaxel containing regimens). Have an Eastern Cooperative Oncology Group Performance status of 0-1. Have ability to swallow tablets. no contraindications to sorafenib or donafenib. Have either measurable or evaluable lesion on CT. Exclusion Criteria: Patients with brain metastases. Patients receiving cytotoxic chemotherapy, immunotherapy or hormonal therapy, radiotherapy to site of measurable or evaluable disease within the previous 4 weeks. Patients had evidence of clinically active interstitial lung disease or abnormal blood results by predefined criteria (serum bilirubin >1.5 times upper limit of reference range, aspartate or alanine aminotransferase>2.5 times the upper limit of normal if no demonstrable liver disease) .

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: donafenib tosilate tablets<br>200mg bid | Drug: donafenib tosilate tablets<br>* 200mg,bid<br>* Other names: CM4307;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events | percentage of any adverse events | 54 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response | Tumor evaluation by investigators according to RECIST 1.1 criteria | 54 weeks | 
| Progression-free survival | PFS was defined as the time from date of randomization to disease progression radiological or death due to any cause, whichever occurs first. Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. | 54 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
donafenib