NCT03290092: TOTEM

Trial of Taselisib in Overgrowth

Terminated Phase 1, PHASE2 Last updated 4 February 2026

What this trial tests

Phase 1, PHASE2 trial testing Taselisib (GDC0032) in PIK3CA-Related Overgrowth in 19 participants. Terminated before completion.

Timeline

31 July 2017

Primary endpoint
14 February 2019

4 November 2019

Quick facts

Lead sponsor	Centre Hospitalier Universitaire Dijon
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	19
Start date	31 July 2017
Primary completion	14 February 2019
Estimated completion	4 November 2019
Sites	18 locations across France

Drugs / interventions tested

• Taselisib (GDC0032) — full drug profile →
• Taselisib (GDC0032) — full drug profile →

Conditions studied

• PIK3CA-Related Overgrowth — all drugs for PIK3CA-Related Overgrowth →

Sponsor

Centre Hospitalier Universitaire Dijon

Who can join

Adults 16 to 65, any sex, with PIK3CA-Related Overgrowth. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
   Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
2. Work-Up and Treatment Strategies for Individuals with <i>PIK3CA</i>-Related Disorders: A Consensus of Experts from the Scientific Committee of the Italian Macrodactyly and PROS Association.
   Gazzin A, Leoni C, Viscogliosi G, Borgini F, et al · · 2023 · cited 9× · PMID 38136956 · DOI 10.3390/genes14122134