TQBSP: TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss

Sponsor

Peking University People's Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04690725

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Safety Issues Efficacy, Self	Drug: TQB3525	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

TQB3525 orally takenTQB3525 orally taken

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 1, 2020

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TQB3525 arm 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 TQB3525 is an orally bioavailable, potent, class I kinase inhibitors of PI3Ka and PI3Kd.

Arm

Intervention/Treatment

Experimental: TQB3525 arm

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

TQB3525 is an orally bioavailable, potent, class I kinase inhibitors of PI3Ka and PI3Kd.

Outcome Measures

Primary Outcome Measures

toxicity profiles [6 months]
according to CTCAE 5.0

Secondary Outcome Measures

progression free survival [6 months]
from starting treatment to progression/death
overall survival [2 years]
from starting treatment to death

Other Outcome Measures

fasting triglyceride [6 months]
dynamic changes from Peripheral Blood
fasting lipoprotein [6 months]
dynamic changes from Peripheral Blood
fasting insulin [6 months]
dynamic changes from Peripheral Blood

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.