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

• ClinicalTrials.gov Identifier: NCT04690725
• Recruitment Status: Unknown
• First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Sponsor: Peking University People's Hospital
• Information provided by (Responsible Party): GUO WEI, Peking University People's Hospital

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 (Clinical Trial)
• Estimated Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: TQB3525 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: October 1, 2020
• Estimated Primary Completion Date: January 1, 2022
• Estimated Study Completion Date: June 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.

Outcome Measures

Primary Outcome Measures :

1. toxicity profiles [ Time Frame: 6 months ]
   according to CTCAE 5.0

Secondary Outcome Measures :

1. progression free survival [ Time Frame: 6 months ]
   from starting treatment to progression/death
2. overall survival [ Time Frame: 2 years ]
   from starting treatment to death

Other Outcome Measures:

1. fasting triglyceride [ Time Frame: 6 months ]
   dynamic changes from Peripheral Blood
2. fasting lipoprotein [ Time Frame: 6 months ]
   dynamic changes from Peripheral Blood
3. fasting insulin [ Time Frame: 6 months ]
   dynamic changes from Peripheral Blood

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China

Peking University Shougang Hospital

Beijing, China, 100036

Sponsors and Collaborators

Peking University People's Hospital

Investigators

• Principal Investigator: Wei Guo, Ph.D and M.D.; Chinese Sarcoma Study Group

More Information

• Responsible Party: GUO WEI, Director, Head of Msculoskeletal Tumor Center, Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT04690725
• Other Study ID Numbers: PKUPH-sarcoma12
• First Posted: December 31, 2020
• Last Update Posted: December 31, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GUO WEI, Peking University People's Hospital:

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

Additional relevant MeSH terms:

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