TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss

Safety Issues Clinical Trial

— TQBSP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04690725
• Other study ID #: PKUPH-sarcoma12
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 1, 2020
• Est. completion date: June 1, 2022

Study information

• Verified date: December 2020
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 29
• Est. completion date: June 1, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Efficacy, Self
• Osteosarcoma
• Safety Issues
• Sarcoma

Intervention

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

Locations

Country	Name	City	State
China	Peking University Shougang Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	fasting triglyceride	dynamic changes from Peripheral Blood	6 months
Other	fasting lipoprotein	dynamic changes from Peripheral Blood	6 months
Other	fasting insulin	dynamic changes from Peripheral Blood	6 months
Primary	toxicity profiles	according to CTCAE 5.0	6 months
Secondary	progression free survival	from starting treatment to progression/death	6 months
Secondary	overall survival	from starting treatment to death	2 years