Ignite Creation Date:
2025-12-24 @ 3:43 PM
Ignite Modification Date:
2026-01-03 @ 8:18 PM
Study NCT ID:
NCT03290092
Status:
TERMINATED
Last Update Posted:
2019-11-12
First Post:
2017-09-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Trial of Taselisib in Overgrowth
Sponsor:
Centre Hospitalier Universitaire Dijon
Organization:
Study Overview
Official Title:
A Multi-Centre, Open Label, Single Arm, Phase IB/IIA, Trial of Taselisib (GDC0032) in PIK3CA-Related Overgrowth
Status:
TERMINATED
Status Verified Date:
2018-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
In accordance with the protocol, following the occurrence of two SUSARs, the TOTEM trial was stopped early for safety reasons.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TOTEM
Brief Summary:
Segmental overgrowth disorders are rare conditions characterised by abnormal growth which is usually asymmetric and confined to discrete parts of the body. We and others have identified mosaic activating mutations in the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K; encoded by the PIK3CA gene) in a subset of overgrowth disorders. The PI3K-AKT-mTOR is a critical signalling pathway, which regulates cellular growth, proliferation and survival. Activating mutations in PIK3CA lead to increased activation of the PI3K-AKT-mTORC1 axis, which in turn promotes excessive growth in affected tissue.
The PIK3CA-related overgrowth spectrum is wide, and depends upon the timing of the founder mutation in embryogenesis, and potentially upon the exact mutation. Clinical presentation ranges from isolated enlargement of a digit, to extensive overgrowth of limbs, abdomen and in some cases the brain, and may be accompanied by vascular or lymphatic malformations. Associated morbidity can be profound, with functional impairment, debilitating haemorrhages and thromboses, coupled with neurological sequelae and, in some cases, death. At present, serial debulking surgery is the only available therapeutic option.
The identification of gain-of-function mutations in PI3K has raised the possibility of treatment with drugs that inhibit PIK3CA (the p110 alpha catalytic subunit of PI3K). Taselisib is a selective inhibitor of class I PI3Ks and has direct inhibitory activity of the p110α isoform with a Kiapp value of 0.29 nmol/l.
The PIK3CA-related overgrowth spectrum is wide, and depends upon the timing of the founder mutation in embryogenesis, and potentially upon the exact mutation. Clinical presentation ranges from isolated enlargement of a digit, to extensive overgrowth of limbs, abdomen and in some cases the brain, and may be accompanied by vascular or lymphatic malformations. Associated morbidity can be profound, with functional impairment, debilitating haemorrhages and thromboses, coupled with neurological sequelae and, in some cases, death. At present, serial debulking surgery is the only available therapeutic option.
The identification of gain-of-function mutations in PI3K has raised the possibility of treatment with drugs that inhibit PIK3CA (the p110 alpha catalytic subunit of PI3K). Taselisib is a selective inhibitor of class I PI3Ks and has direct inhibitory activity of the p110α isoform with a Kiapp value of 0.29 nmol/l.
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: