Clinical trial NCT04671849: An Open Label, Multi-center, Phase I Clinical Study to Evaluate 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.
Official title: An Open Label, Multi-center, Phase I Clinical Study to Evaluate 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors With NTRK, ROS1 or ALK Gene Fusion
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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；

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 5 years
measure: Severity of adverse events
timeFrame: 5 years
measure: Maximum tolerated dose
timeFrame: 5 years
measure: Recommended dose for dose expansion
timeFrame: 5 years
measure: Maximum concentration of SIM1803-1A in plasma (Cmax)
timeFrame: 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）
measure: Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to 24 hours in fasted state (AUC(0-24)_fasted)
timeFrame: Up to 1 day
measure: Area under the concentration-time curve of SIM1803-1A in plasma from time 0 to infinity in fasted state (AUC_fasted)
timeFrame: Up to 3 days
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: Up to 24 weeks
measure: Time to maximum concentration of SIM1803-1A in plasma (Tmax)
timeFrame: 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)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 60 months
measure: Duration of Response (DOR)
timeFrame: Up to 60 months
measure: progression-free survival（PFS）
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
Study officials:
affiliation: Shanghai Chest Hospital
name: shun lu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: