To Evaluate KC1036 in the Patients With Advanced Digestive System Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the preliminary efficacy, safety, tolerability and pharmacokinetics of KC1036 in participants with advanced recurrent or metastatic digestive system tumors.

Detailed Description
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This is an open label, non-randomized，phase 1b/2 study to explore the preliminary antitumor activity of KC1036 in patients with advanced recurrent or metastatic digestive system tumors under BID or QD regimen. The study will consist of two parts: Part 1: QD regimen To evaluate the efficacy and safety of KC1036 in the treatment of advanced recurrent, unresectable and / or metastatic digestive system tumors under 60mg QD regimen. Part 2: BID regimen Dose-Escalation part : To explore the safety of KC1036 under 20mg BID, 30mg BID and 40mg BID in patients with advanced recurrent or metastatic digestive system tumors. Dose-Expansion part : According to the results of Dose-Escalation, an appropriate BID regimen was selected for Dose-Expansion to evaluate the effectiveness and safety of KC1036 in patients with advanced recurrent, unresectable and / or metastatic digestive system tumors.

Official Title
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A Phase Ib / II Study to Evaluate the Efficacy and Safety of KC1036 in the Patients With Advanced Recurrent or Metastatic Digestive System Tumors

Conditions
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Digestive System Tumors

Intervention / Treatment
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* Drug: KC1036


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed malignant digestive system tumors; Patients with advanced recurrent, unresectable and / or metastatic digestive system tumors who have failed standard or conventional treatment:( definition of treatment failure: intolerable toxic and side effects, disease progression during treatment recurrence after treatment); Eastern Cooperative Oncology Group performance status score of 0 or 1; Life expectancy > 12 weeks; BMI≥18.0; Has adequate Hematologic, renal, and hepatic function; Patients should participate in the study voluntarily and sign informed consent. Exclusion Criteria: Any patient who is known to have central nervous system (CNS) metastasis with clinical symptoms; Other kinds of malignancies; Gastrointestinal abnormalitiest; Cardiovascular and cerebrovascular diseases; Previous treatment with small molecule vascular targeting inhibitor； Prior anti-tumor therapies with chemotherapy, radiotherapy, hormonotherapy, biotherapy, immunotherapy, operation within 4 weeks before enrollment; Involved in other clinical trials within 4 weeks before enrollment; Major surgical procedure, open biopsy, or significant traumatic injury 4 weeks before enrollment; Uncontrolled massive ascites,pleural/pericardial effusion; Uncontrolled ongoing or active bacterial, viral or fungal infectious; Fever of unknown cause (> 38.5 ℃) occurred within 2 weeks before enrollment; Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection ; Pregnant or lactating women or those who do not take contraceptives, including men; Any other metabolic dysfunction, abnormal physical examination findings, or clinical laboratory findings; Inability to comply with protocol required procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QD regimen<br>KC1036 was administered orally in 60 mg once daily, 21 days as a cycle. | Drug: KC1036<br>* KC1036 are administered orally QD or BID in 21-day cycles.<br>|
| Experimental: BID regimen<br>Dose-Escalation part : KC1036 was administered orally in 20 mg BID, 30 mg BID, or 40 mg BID. Dose-Expansion part : According to the results of Dose-Escalation, an appropriate BID regimen was selected for Dose-Expansion . | Drug: KC1036<br>* KC1036 are administered orally QD or BID in 21-day cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Overall response rate (ORR) was defined as the percentage of participants with a best overall complete response (CR) or partial response (PR) per RECIST 1.1. | approximately 2 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival (PFS) was defined as the time from the start date of study drug to the date of the first radiologically documented progressive disease (PD) per RECIST 1.1 or death due to any cause. | approximately 2 year | 
| Disease Control Rate (DCR) | Disease Control Rate (DCR) was defined as the percentage of participants with a best overall complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1. | approximately 2 year. | 
| Duration of Response (DOR) | Duration of response (DOR) was defined as the time from first documented response (partial response (PR) or complete response (CR)) to the date of first documented disease progression (PD) or death due to any cause, among patients with a confirmed PR or CR per RECIST 1.1. | approximately 2 year. | 
| Pharmacokinetics (PK) profile: Cmax | Parameters: Peak Plasma Concentration | approximately 2 year. | 
| Pharmacokinetics (PK) profile: Tmax | Parameters: Time to reach the maximum plasma concentration | approximately 2 year. | 
| Pharmacokinetics (PK) profile: T1/2 | Parameters: Terminal half-life | approximately of 2 year. | 
| Pharmacokinetics (PK) profile: AUC | arameters: Area under the single-dose plasma concentration-time curve. | approximately of 2 year. | 
| Adverse events (AEs) | Incidence of treatment-related AEs | approximately of 2 year. |