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

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

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.

Study Overview

• Status: Unknown
• Conditions: Safety Issues; Efficacy, Self
• Intervention / Treatment: Drug: TQB3525

• Study Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100036
    • Peking University Shougang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
fasting triglyceride	dynamic changes from Peripheral Blood	6 months
fasting lipoprotein	dynamic changes from Peripheral Blood	6 months
fasting insulin	dynamic changes from Peripheral Blood	6 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Wei Guo, Ph.D and M.D., Chinese Sarcoma Study Group

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2020
• Primary Completion (ANTICIPATED): January 1, 2022
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: December 25, 2020
• First Submitted That Met QC Criteria: December 29, 2020
• First Posted (ACTUAL): December 31, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 31, 2020
• Last Update Submitted That Met QC Criteria: December 29, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: osteosarcoma; chondrosarcoma; PTEN loss; ewing sarcoma; PI3KA mutation; TQB3525
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma
• Other Study ID Numbers: PKUPH-sarcoma12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No