Adenocarcinoma of Esophagogastric Junction, Basal Cell Carcinoma, Glioblastoma, Medulloblastoma, Neuroendocrine Neoplasm, Small Cell Lung Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics, and determine the maximum tolerated dose of ZSP1602 in participants with basal cell carcinoma, adenocarcinoma of esophagogastric junction, small cell lung cancer, neuroendocrine neoplasm and other advanced solid tumors.
Interventions
DRUGZSP1602
ZSP1602 capsules for oral administration
Sponsors
Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants are required to meet all the criteria below in order to be included in the trial: 1. Male or female participants, aged 18 \ 75 years. Confirmed diagnosis of advanced solid tumors by histological or cytological examination, Participants have no effective standard anticancer therapy available or is intolerant to standard anticancer therapy. For Part 1 Dose Ascending Stage, and Part 2 Dose expansion Stage: For Part 1: Advanced solid tumors including basal cell carcinoma and medulloblastoma, regardless of SMO or Gli1 alteration status. For Part 2: Participants will be enrolled into cohort A and cohort B. Cohort A: Participants with Adenocarcinoma of Esophagogastric Junction with SMO or Gli1 protein overexpression alteration. (IHC≥1%) Cohort B: Participants with basal cell carcinoma, small cell lung cancer, neuroendocrine neoplasm and glioblastoma with SMO or Gli1 protein overexpression alteration. (IHC≥1%) 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 3. Participants with at least 1 measurable tumor lesion based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and response assessment in neuro-oncology criteria (RANO) (participants with glioblastoma must accept skull MRI scanning.) 4. Recovery from past medical history of adverse reactions (excluding alopecia and neurotoxicity) caused by radiotherapy and chemotherapy to national cancer institute common terminology criteria for adverse events 4.03 (NCI CTCAE 4.03) ≤Grade 1 or baseline level. 5. Life expectancy \> 12 weeks. 6. Adequate organ function, defined by the following laboratory results, to be obtained prior to registration and enrollment: Bone marrow function: absolute neutrophil count (ANC)≥1.5×10\^9/L; hemoglobin (HB)≥90 g/L; Platelet count (PLT)≥75×10\^9/L. Liver function: Alanine aminotransferase (ALT)≤2.5×the upper limit of normal (ULN), aspartate aminotransferase (AST)≤2.5×ULN, alkaline phosphatase (ALP)≤2.5×ULN, total bilirubin (TBIL)≤1.5×ULN; ALT≤5×ULN, AST≤5×ULN, ALP≤5×ULN (For participants with liver metastasis). Renal function: creatinine≤1.5×ULN; clearance (CL)≥ 60 mL/min. Coagulation function: international normalized ratio (INR)≤1.5×ULN, activated partial thromboplastin time (APTT)≤1.5×ULN. Left ventricular ejection fractions (LVEF)≥50%. Creatine kinase (CK)≤2.5×ULN. 7. Participants (including partners) have no gestation plans and must use reliable methods of contraception during the study and until 8 months following the last dose of investigational product. 8. Participants must provide a written dated Informed Consent Form (ICF) with signature prior to screening. 9. Participants must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.
Exclusion criteria
* Eligible participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting Toxicity (DLT) | At day 32 after first dosing. | To determine the DLT of ZSP1602 in advanced solid tumor participants accessed by CTCAE4.03 |
| Maximum tolerated dose (MTD) | At day 32 after first dosing. | The highest dose at the level with \<= 2/6 participants experienced DLT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of ZSP1602 | Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants. | For Part1 and Part2 |
| Tmax of ZSP1602 | Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants. | For Part1 and Part2 |
| Cmin of ZSP1602 | Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants. | For Part1 and Part2 |
| Time to progression (TTP) | From Screening, Day 28 of Cycle1 (28 days), then every 8 weeks, until disease progression or discontinuation from study (approximately 18 months or earlier if participants terminate from the study). | For Part1 and Part2 |
| T1/2 of ZSP1602 | Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants. | For Part1 and Part2 |
| Cl/F of ZSP1602 | Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants. | For Part1 and Part2 |
| AUC0-t of ZSP1602 | Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants. | For Part1 and Part2 |
| Over all response (ORR) | From Screening, Day 28 of Cycle1 (28 days), then every 8 weeks, until disease progression or discontinuation from study (approximately 18 months or earlier if participants terminate from the study). | For Part1 and Part2 |
Countries
China
Contacts
Primary ContactYing Cheng, MD
Outcome results
None listed