TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss

Study Overview
=================
Brief Summary
-----------------
The PI3K, protein kinase B (AKT), and mTOR signaling network promotes cell growth, survival, metabolism, and motility, but becomes a critical oncogenic driver under aberrant conditions that control the tumor microenvironment and angiogenesis. The PI3K-AKT-mTOR axis is the most frequently deregulated signaling pathway in primary osteosarcoma and other bone tumors. PI3Ka has high rates of 25-50% activating mutations associated with tumor formation in osteosarcoma. Other causes of pathway hyperactivation include loss of function of the tumor suppressor PTEN, gain-of-function mutations in AKT and PDK1, or upregulation of receptor tyrosine kinases. TQB3525 is an orally bioavailable, potent, dual catalytic site inhibitor of PI3Ka and PI3Kd. Tumor growth inhibition has been demonstrated in multiple xenograft osteosarcoma models with PI3K-mutant, PTEN-null cell lines. The investigators try to investigate TQB3525 in primary osteosarcoma and other bone tumors for its safety, tolerability, dose-limiting toxicities (DLT), MTD and antitumor efficacy.

Official Title
-----------------
Phase I Study of TQB3525, Phosphatidylinositol-3-Kinase α and δ Inhibitors, in Patients With Advanced Bone Sarcomas

Conditions
-----------------
Safety Issues, Efficacy, Self

Intervention / Treatment
-----------------
* Drug: TQB3525


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: progression upon first-line chemotherapy; with target lesions according to RECIST 1.1; geno-profiling with PI3KA mutations or PTEN loss; ECOG PS status 0 or 1 with a life expectancy >3 months; adequate renal, hepatic, and hematopoietic function; Exclusion Criteria: been previously exposed to other TKIs; had central nervous system metastasis; had other kinds of malignant tumors at the same time; had cardiac insufficiency or arrhythmia; had uncontrolled complications such as diabetes mellitus, coagulation disorders, urine protein ≥ ++, and so on; had pleural or peritoneal effusion that needed to be handled by surgical treatment; had other infections or wounds; pregnant or breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: TQB3525 orally taken
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB3525 arm<br>3+3 design for phase I for RP2D (Recommended Phase 2 Dose) for adolescents (12-17 years old) (15mg QD or 20mg QD); phase II for efficacy exploration for another 17 patients using RP2D QD | Drug: TQB3525<br>* TQB3525 is an orally bioavailable, potent, class I kinase inhibitors of PI3Ka and PI3Kd.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| toxicity profiles | according to CTCAE 5.0 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | from starting treatment to progression/death | 6 months | 
| overall survival | from starting treatment to death | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteosarcoma, ewing sarcoma, chondrosarcoma, PI3KA mutation, PTEN loss, TQB3525