Advanced or Metastatic Solid Tumors With NTRK, ROS1 or ALK Gene Fusion
Conditions
Brief summary
This research study is done to test the safety, effectiveness and pharmacokinetic characteristics of SIM1803-1A in patients with locally advanced/metastatic solid tumors with NTRK, ROS1 or ALK gene fusion mutations. The cancer must have a change in a particular gene (NTRK1, NTRK2, NTRK3, ROS1 or ALK). SIM1803-1A is a drug that blocks the actions of these NTRK/ ROS1 /ALK genes in cancer cells and can therefore be used to treat cancer.
Interventions
DRUGSIM1803-1A
SIM1803-1A will be administered orally as tablets at a given dose once daily in continuing 21-days cycles.
Sponsors
Jiangsu Simcere Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists；Proof of a malignancy harboring a NTRK、ROS1 or ALK fusion；Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 and a life expectancy of at least 3 month；Adequate hematologic, hepatic, and renal function；Signed informed consent form；
Exclusion criteria
* Any contraindications as listed in the local approved product information；Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible；Pregnancy or lactation；Clinically significant active cardiovascular disease or history of myocardial infarction；Participation in an investigational program with interventions outside of routine clinical practice；Prior treatment with other kinase inhibitor with tropomyosin receptor kinase inhibition；Active uncontrolled systemic bacterial, viral, or fungal infection；Current treatment with a strong CYP3A4 inhibitor or inducer；
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to maximum concentration of SIM1803-1A in plasma (Tmax) | Predose and 0.25, 0.5, 1, 2, 4, 8，12，24and 48 hours after drug administration on Days 1 and 8 of Cycle 1（each cycle is 21 days) | Time to maximum concentration of SIM1803-1A in plasma (Tmax) |
| Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)_fasted) | Up to 1 day | Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)\_fasted) |
| Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to infinity in fasted state (AUC_fasted) | Up to 3 days | Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to infinity in fasted state (AUC\_fasted) |
| Number of participants with treatment-emergent adverse events (TEAEs) | Up to 24 weeks | Number of participants with treatment-emergent adverse events (TEAEs) |
| Number of participants with adverse events | 5 years | Number of participants with adverse events |
| Severity of adverse events | 5 years | Severity of adverse events |
| Maximum tolerated dose | 5 years | Maximum tolerated dose |
| Recommended dose for dose expansion | 5 years | Recommended dose for dose expansion |
| Maximum concentration of SIM1803-1A in plasma (Cmax) | Predose and 0.25, 0.5, 1, 2, 4, 8，12，24and 48 hours after drug administration on Days 1 and 8 of Cycle 1（each cycle is 21 days） | Maximum concentration of SIM1803-1A in plasma (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to 60 months | Duration of Response (DOR) |
| progression-free survival（PFS） | Up to 60 months | progression-free survival（PFS） |
| Overall Response Rate (ORR) | Up to 60 months | Overall Response Rate (ORR) |
Countries
China
Contacts
Primary Contactzhen zhou, MD
Outcome results
None listed