Trial of Taselisib in Overgrowth (TOTEM)

February 2, 2026 updated by: Centre Hospitalier Universitaire Dijon

A Multi-Centre, Open Label, Single Arm, Phase IB/IIA, Trial of Taselisib (GDC0032) in PIK3CA-Related Overgrowth

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
19

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49933
        • CHU d'Angers
      • Bordeaux, France, 33076
        • CHU de Bordeaux - GH Pellegrin
      • Dijon, France, 21000
        • CHU Dijon Bourgogne
      • Garches, France, 92380
        • Hôpital Raymond Poincaré (AP-HP)
      • Lille, France, 59037
        • Hôpital Jeanne de Flandre
      • Lyon, France
        • HCL - Hôpital femme-mère-enfant
      • Montpellier, France, 34295
        • Hopital Saint Eloi
      • Montpellier, France, 34090
        • Hopital Arnaud de Villeneuve
      • Nantes, France, 44093
        • Chu Hotel Dieu
      • Nice, France, 06202
        • CHU de Nice - Hôpital L'Archet 2
      • Paris, France, 75743
        • Hôpital Necker-Enfants Malades
      • Rennes, France, 35203
        • Hopital Sud
      • Saint-Pierre, France, 97448
        • CHU La Réunion - Site GHSR
      • Saint-Priest-en-Jarez, France, 42270
        • CHU de Saint-Etienne Hôpital Nord
      • Toulouse, France, 31059
        • Hôpital Larrey
      • Tours, France, 37044
        • Hôpital Trousseau
      • Vandœuvre-lès-Nancy, France, 54511
        • CHU de Nancy
      • Vandœuvre-lès-Nancy, France, 54511
        • CHU de Nancy - Hopital de Brabois

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 61 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have given, or their legal representative has given, written informed consent to participate
  • Aged 16 years to 65 years inclusive
  • Male or female
  • Post-zygotic PIK3CA mutation
  • Clinically stable in the opinion of the investigator

  • Participant Pregnancy and contraception:

    o Female participants of child bearing potential must use an effective method of contraception during treatment and for at least 3 months after the final dose of taselisib. Acceptable methods are:

  • True abstinence (this must be the participant's usual and preferred lifestyle, not just for the duration of the trial)
  • Oral contraceptive (either combined or progestogen alone)
  • Contraceptive implant, injections or patches
  • Vaginal ring
  • Intrauterine device (IUD, coil or intrauterine system)
  • Condom and cap

  • Diaphragm plus spermicide

    • A female participant of child bearing potential is defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 12 consecutive months if aged 55 years or older.
    • Men must use one of the following, reliable forms to contraception for the entire duration of treatment and for 3 months after the final dose of taselisib:
  • Condom plus spermicide even if female partner is using another method of contraception (Men should also use a condom to protect male partners, or female partners who are pregnant or breast feeding, from exposure to the Trial medicine in semen).
  • True abstinence (this must be the participant's usual and preferred lifestyle, not just for the duration of the Trial)

Exclusion Criteria:

  • Pregnant or breastfeeding
  • HIV infection
  • Hypersensitivity to taselisib or any of its excipients
  • Any current medical disorder or medication likely to impair ability to follow the trial protocol safely and effectively
  • Are concurrently taking an mTOR inhibitor or any other small molecule inhibitor of the PI3K-AKT signalling pathway
  • Unable or unwilling to give informed consent
  • Sirolimus or taselisib treatment in 12 weeks prior to screening
  • Treatment with a strong inducer or inhibitor of CYP3A4 without the possibility to stop this medication within the week prior to the screening. This includes:
  • Macrolide Antibiotics: clarithromycin, telithromycin, erythromycin, troleandomycin
  • Gastrointestinal prokinetic agents: metoclopramide.
  • Antifungals: itraconazole, ketoconazole, fluconazole, voriconazole, clotrimazole
  • Calcium channel blockers: verapamil, diltiazem, nicardipine
  • Grapefruit containing foods/drinks
  • Anticonvulsants: carbamazepine, phenobarbital, phenytoin
  • Antibiotics: rifampicin, rifabutin, rifapentine
  • Herbal preparations: St. John's wort (Hypericum perforatum). Other drugs: bromocriptine, cimetidine, danazol, cyclosporine, lansoprazole, calcium containing antacids.
  • Inability to attend trial visits
  • If less than 3 months post- major surgery at screening
  • Any past medical history of inflammatory bowel disease or chronic diarrhoea of unknown aetiology
  • History of type 1 or type 2 diabetes mellitus requiring insulin, GLP-1 analogues or oral hypoglycaemic agents.
  • History of inflammatory bowel disease, ischemic colitis, or colitis of unknown origin.
  • Fasting blood glucose > 6.9 mmol/l
  • HbA1C > 6%
  • Long QT, congenital or acquired
  • Active pneumonitis
  • Patients who require daily supplemental oxygen
  • Inadequate renal function defined as creatinine clearance or radioisotope GFR < 60ml/min/1.73 m²
  • Inadequate liver function defined as:
  • Total bilirubin > 2.0 x ULN or conjugated bilirubin > 2.0 x ULN for age, and
  • SGPT (ALT) or SGOT (AST) ≥ 1.5 x ULN for age, and
  • Serum albumin < 30 g/L
  • Inadequate fasting LDL cholesterol > 4.2 mmol/l
  • Deprived of freedom by an administrative or court order, or benefiting from a system of legal protection (tutorship, curatorship or safeguard of justice).
  • Not covered by health insurance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment
Drug: Taselisib (GDC0032)
The first six participants cohort receive a starting dose of 1mg once daily of taselisib during four weeks.
Drug: Taselisib (GDC0032)
The starting dose of the second cohort of 24 patients is 2 mg once daily. This dose may be adjusted down according to the pharmacokinetic data or tolerability data derived from the first cohort.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Occurrence of dose limiting toxicities
Time Frame: less than 24 hours

The dose limiting toxicity (DLT) is defined as a Grade 3 or more AE using the National Cancer Institute (NCI).

If two out of up to six participants at the same dose level experience a DLT as defined above, subsequent cohorts will be dosed at a lower level as illustrated in the flow-chart below. At least six evaluable participants are required to establish the MTD (Maximum tolerated dose) at a specific dose level for both combinations.
less than 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire Dijon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 31, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 14, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 4, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 19, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • OLIVIER-FAIVRE ROCHE 2016

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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