HER2-positive Advanced Solid Tumors
Conditions
Brief summary
To evaluate the safety and tolerability of SPH5030 tablets in subjects with HER2-positive advanced solid tumors
Interventions
DRUGSPH5030 tablets
SPH5030 tablets orally once or twice daily.
Sponsors
Shanghai Pharmaceuticals Holding 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
1. ECOG performance status of 0 to 1. 2. Life expectancy of more than 3 months. 3. At least one measurable lesion exists.(RECIST 1.1) 4. Histologically or cytologic confirmed HER2 positive metastatic solid tumor which failed prior standard treatment or have no standard treatment. 5. Required laboratory values including following parameters: ANC: ≥ 1.5 x 109/L Plt count: ≥ 90x 109/L Hb: ≥ 90 g/L TBIL: ≤ 1.5 x ULN, ALT and AST: ≤ 2.5 x ULN and creatine clearance rate: ULN or≥ 50 mL/min 6. Toxicity from previous antitumor therapy returned to baseline (except for residual hair loss effects) or CTCAE≤ class 1. 7. Blood pregnancy test was negative within 3 days prior to first dose.
Exclusion criteria
1. Subjects who have received the prescribed treatment at the prescribed time prior to first dosing. 2. Known active infection within 2 weeks prior to baseline. 3. Subjects with third space fluid that can not be controled. 4. Subjects with uncontrolled or severe cardiovascular disease. 5. Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry. 6. Subjects with severe lung disease. 7. Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption. 8. Using a potent CYP3A4 or CYP2C8 inhibitor or inducer. 9. Steroid treatment for more than 50 days before, or in need of long-term use of steroids. 10. Uncured other tumors within 5 years. 11. Subjects with symptomatic CNS metastasis, pia meningeal metastasis, or spinal cord compression due to metastasis. 12. Evidence of chronic active hepatitis B or C 13. Uncontrolled systemic diseases, including hypertension that cannot be effectively controlled after treatment. 14. Receive any live or attenuated live vaccine within 28 days prior to baseline. 15. Evidence of severe allergies. 16. Evidence of alcohol or drug abuse. 17. Evidence of neurological or psychiatric disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Up to 24 days | Measurement of DLT of SPH5030 in all subjects |
| Maximum tolerated dose（MTD） | Up to 24 days | Measurement of MTD of SPH5030 in all subjects |
| Number of patients with adverse events | Up to 2 years | Adverse event type, incidence, duration, correlation with study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum serum concentration (Cmax) of SPH 5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Time of maximum serum concentration (Tmax) SPH 5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-Last) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Accumulation ratio of maximum serum concentration (Rac_Cmax) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Accumulation ratio of area under the serum concentration-time curve (Rac_AUC) of the Dosing Interval (0-14D) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Terminal rate constant(λz) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Half-life (t1/2) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Total clearance(CL) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Volume of distribution(Vz) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Percentage of area under the serum concentration-time curve (AUC) obtained by extrapolation (%AUCex) of SPH5030 | Up to 2 years | To characterize the PK (Pharmacokinetics) of SPH 5030 |
| Objective Response Rate (Investigator) | Up to 2 years | Determination of the Objective Response Rate of all patients by investigators |
| Duration of remission (DOR) | Up to 2 years | Time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review as per RECIST v1.1. |
| Disease control rate (DCR) | Up to 2 years | The proportion of patients with best confirmed RECIST response of CR, PR, or duration of SD. |
| Progression-free survival (PFS) | Up to 2 years | The interval between the dates of the first dose of trial treatment until first documentation of disease progression or death, whichever occurs first. |
| 6-month Progression-free Survival (6mPFS) | Up to 2 years | Number of Patients Achieving 6-month Progression-free Survival |
Countries
China
Contacts
CONTACTXingchen Wang
PRINCIPAL_INVESTIGATORBinghe Xu
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed