To Evaluate KC1036 in the Patients With Advanced Digestive System Tumors
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
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 1: 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: QD regimen 60mg QD |
Drug: KC1036
Patients take a single dose （60mg QD）of KC1036 for the efficacy and safety study. KC1036 are given orally once daily, 21 days as a cycle.
|
| Experimental: BID regimen Dose-Escalation part : 20mg BID, 30mg BID and 40mg BID. Dose-Expansion part : According to the results of Dose-Escalation, an appropriate BID regimen was selected for Dose-Expansion . |
Drug: KC1036
Dose-Escalation part: Patients take a two dose（20mg BID、30mg BID and 40mg BID）of KC1036 for the pharmacokinetic and safety study. KC1036 are given orally twice daily, 21 days as a cycle.
Dose-Expansion part : According to the results of Dose-Escalation, an appropriate BID regimen was selected for Dose-Expansion of KC1036 for the efficacy and safety study.KC1036 are given orally twice daily, 21 days as a cycle.
|
Outcome Measures
Primary Outcome Measures
- Progression-free survival (PFS) [approximately 2 year]
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.
- Objective Response Rate (ORR) [approximately 2 year.]
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.
Secondary Outcome Measures
- Disease Control Rate (DCR) [approximately 2 year.]
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.
- Duration of Response (DOR) [approximately 2 year.]
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.
- Pharmacokinetics (PK) profile: Cmax [approximately 2 year.]
Parameters: Peak Plasma Concentration
- Pharmacokinetics (PK) profile: Tmax [approximately 2 year.]
Parameters: Time to reach the maximum plasma concentration
- Pharmacokinetics (PK) profile: T1/2 [approximately of 2 year.]
Parameters: Terminal half-life
- Pharmacokinetics (PK) profile: AUC [approximately of 2 year.]
arameters: Area under the single-dose plasma concentration-time curve.
- Adverse events (AEs) [approximately of 2 year.]
Incidence of treatment-related AEs
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed malignant digestive system tumors;
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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);
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Eastern Cooperative Oncology Group performance status score of 0 or 1;
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Life expectancy > 12 weeks;
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BMI≥18.0;
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Patients should participate in the study voluntarily and sign informed consent.
Exclusion Criteria:
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Any patient who is known to have central nervous system (CNS) metastasis or imaging shows a risk of CNS metastasis;
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Other kinds of malignancies;
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Hematologic, renal, and hepatic function abnormities;
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Risk of bleeding;
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Gastrointestinal abnormalitiest;
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Cardiovascular and cerebrovascular diseases;
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Disease progression after previous treatment with PD-1 / PD-L1 antibody combined with small molecule vascular targeting inhibitor；Prior anti-tumor therapies with chemotherapy, radiotherapy, hormonotherapy, biotherapy, immunotherapy, operation within 4 weeks before enrollment;
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Presence of unresolved toxicities from prior anti-tumor therapy, defined as having not resolved to NCI CTCAE V5.0 grade 0 or 1 with the exception of alopecia, ≤ grade 2 neuropathy, non clinically significant and asymptomatic laboratory abnormalities;
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Involved in other clinical trials within 4 weeks before enrollment;
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Major surgical procedure, open biopsy, or significant traumatic injury 4 weeks before enrollment;
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History of organ allograft ;
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Need immunosuppressive agents or hormone therapy for immunosuppression, and still need immunosuppressive therapy within 2 weeks before enrollment;
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Uncontrolled ongoing or active bacterial, viral or fungal infectious; Fever of unknown cause (> 38.5 ℃) occurred within 2 weeks before enrollment; Known history or evidence of interstitial lung disease or non infectious pneumonia treated with corticosteroids;
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Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy;
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Pregnant or lactating women or those who do not take contraceptives, including men;
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Suffering from mental and neurological diseases;
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Any other metabolic dysfunction, abnormal physical examination findings, or clinical laboratory findings;
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Inability to comply with protocol required procedures.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Beijing Konruns Pharmaceutical Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KC1036-II-01