Advanced Solid Tumors
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of SKLB1028 in patients with advanced solid tumors.
Detailed description
This study is divided into two stages. The first stage is the dose-escalation stage to evaluate the safety, tolerance and pharmacokinetics of SKLB1028 in patients with advanced solid tumors. A classic 3+3 design will be used to determine the maximum tolerated dose (MTD). Patients with advanced solid tumors will receive SKLB1028 orally once daily (QD) in continuous 28-day cycles, starting at a dose of 200 mg and rising to 400 mg. The second stage is cohort-expansion study. The safe tolerated dose group will be selected for case expansion. At this stage, patients with advanced solid tumors with better response on SKLB1028 are mainly enrolled.
Interventions
DRUGSKLB1028
SKLB1028 capsules, oral, once daily in continuous 28-day cycles
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients volunteered to participate in this study and signed the informed consent form. * Age ≥18, no gender limitation. * Patients with malignant solid tumor who have failed or could not tolerate standard treatment and for whom no standard treatment is available. * Recurrent or metastatic solid tumors confirmed by histology; patients who are judged by the investigator to be suitable for treatment with SKLB1028 capsules and who meet the requirements of tumor type for corresponding stages: 1. Stage I: no restriction on solid tumor types; 2. Phase II: solid tumor type determined by the investigator and the sponsor based on the results of phase I. * Stage 1: At least one unmeasurable lesion; Stage 2: At least one measurable lesion according to RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Patient must meet the following criteria as indicated on the clinical laboratory tests: 1. Absolute neutrophil count ≥1.5×10\^9 /L; platelet count ≥80×10\^9 /L; hemoglobin ≥90 g/L; 2. Serum creatinine ≤ 1.5 × upper limit of normal (ULN); 3. Total bilirubin ≤ 1.5 × ULN, (≤ 3 × ULN for patients with liver metastasis or liver cancer); Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (≤ 5 × ULN for patients with liver metastasis or liver cancer). * Patient is suitable for oral administration of the study drug. * Female patients should agree to use contraceptive measures (such as IUD, condom, etc.) during the study period and within 6 months after the end of the study; negative serum pregnancy test within 7 days prior to enrollment and must be non-lactating patients; male patients should agree to use contraceptive measures during the study period and within 6 months after the end of the study period.
Exclusion criteria
* The patient have a previous history of severe allergy to drugs and food. * Expected survival \< 3 months. * Other malignant active tumors within the past 3 years; except for cured locally curable cancers, such as basal or squamous cell skin carcinoma, or in situ prostate, cervical or breast cancer. * Central nervous system metastasis (excluding brain metastasis with stable symptoms after local treatment) * Patients with hepatitis B (HBsAg positive or HBcAb positive with HBV DNA higher than the upper limit of the normal value of the research center) or hepatitis C (HCV antibody positive with HCV RNA higher than the upper limit of the normal value of the research center) or HIV antibody positive. * Patients whose toxicity of previous anti-tumor treatment has not recovered to ≤ grade 1. * Cardiac dysfunction, including: QTc interval female ≥ 470 ms, male ≥ 450 ms; Complete left bundle branch block, grade II or III atrioventricular block; Poorly controlled malignant arrhythmias; Cardiac valve regurgitation or stenosis requiring treatment; Cardiac ejection fraction less than 50% within 6 months before screening; Myocardial infarction, unstable angina pectoris, severe pericardial disease, severe myocardial disease occurred within 6 months before screening; History of chronic congestive heart failure with NYHA ≥ grade 3. * Patients have poorly controlled hypertension. * Patients have thrombotic or embolic events such as cerebrovascular accident, pulmonary embolism, etc within 6 months before screening. * Patients who have received any antitumor treatment within 4 weeks before the first administration; those who have received herbal or proprietary Chinese medicines with a clear antineoplastic indication 2 weeks prior to the first administration. * Patients have received other unlisted clinical study drugs within 4 weeks before the first administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | At the end of Cycle 1 (each cycle is 28 days) | To identify the maximum tolerated dose (MTD） |
| Dose limiting toxicity (DLT) | At the end of Cycle 1 (each cycle is 28 days) | To identify the dose-limited toxicity (DLT). |
| Treatment Emergent Adverse Event (TEAE) | From the initiation of the first dose to 28 days after the last dose | TEAE is defined as an adverse event that occurs during treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Up to approximately 2 years | ORR is defined as the proportion of patients who have a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. |
| Progression-free survival (PFS) | Up to approximately 2 years | PFS is defined as the time from the date of first dose until the date of first documented PD as per RECIST 1.1 or death from any cause, whichever occurs first |
| Pharmacokinetic indexes, Cmax | At the end of Cycle 1 (each cycle is 28 days) | Maximum concentration (Cmax) of SKLB1028 |
| Duration of response (DOR) | Up to approximately 2 years | DoR is defined as the time from the first assessment of CR or PR until the date of first occurrence of progressive disease (PD) as per RECIST 1.1 or death from any cause, whichever occurs first |
| Disease control rate (DCR) | Up to approximately 2 years | DCR is defined as the proportion of patients who have a response of CR/PR or stable disease (SD) as per RECIST 1.1 |
| Pharmacokinetic indexes, Tmax Pharmacokinetic indexes, Tmax | At the end of Cycle 1 (each cycle is 28 days) | Time to Cmax (Tmax) of SKLB1028 |
| Pharmacokinetic indexes, AUC0-t | At the end of Cycle 1 (each cycle is 28 days) | Area under the concentration-time curve (AUC) from 0 to the last measurable concentration (AUC0-t) of SKLB1028 |
Countries
China
Contacts
Primary ContactXuefang Xia
Outcome results
None listed