TQB3525 for Advanced Bone Sarcomas With PI3KA Mutations or PTEN Loss

NCT04690725 | Unknown Phase 1 DMC

• 1 other identifier: PKUPH-sarcoma12
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Safety Issues; Efficacy, Self

Keywords

osteosarcoma; ewing sarcoma; chondrosarcoma; PI3KA mutation; PTEN loss; TQB3525

Outcome Measures

Primary Outcomes (1)

• toxicity profiles

  according to CTCAE 5.0

  6 months

Secondary Outcomes (2)

• progression free survival

  6 months

• overall survival

  2 years

Other Outcomes (3)

• fasting triglyceride

  6 months

• fasting lipoprotein

  6 months

• fasting insulin

  6 months

Study Arms (1)

TQB3525 arm

EXPERIMENTAL

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

Interventions

TQB3525 DRUG

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

TQB3525 arm

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University Shougang Hospital

Beijing, 100036, China

Location

MeSH Terms

Conditions

Osteosarcoma; Sarcoma, Ewing; Chondrosarcoma

Interventions

TQ-B3525

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Wei Guo, Ph.D and M.D.

  Chinese Sarcoma Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Msculoskeletal Tumor Center

Model Details: TQB3525 orally taken

Study Record Dates

• First Submitted: December 25, 2020
• First Posted: December 31, 2020
• Study Start: October 1, 2020
• Primary Completion: January 1, 2022
• Study Completion: June 1, 2022
• Last Updated: December 31, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)