A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of PQR309

Conditions

Advanced Solid Tumors

Brief summary

This study is a Phase I, open label study to determine the Maximum Tolerated Dose(MTD) and the Recommended Phase II Dose (RP2D) in patients with advanced solid tumors.

Wicki A, Brown N, Xyrafas A, Bize V, Hawle H, Berardi S, Cmiljanović N, Cmiljanović V, Stumm M, Dimitrijević S, Herrmann R, Prêtre V, Ritschard R, Tzankov A, Hess V, Childs A, Hierro C, Rodon J, Hess D, Joerger M, von Moos R, Sessa C, Kristeleit R.

2018-04-1351 citations

10.1016/j.ejca.2018.03.012

Population pharmacokinetics of PQR309, a dual PI3K/mTOR inhibitor in adult patients with advanced solid tumors.

Matthias Macháček, Lionel Renaud, Saša Dimitrijević, Debora Schmitz, Elena V. Ivanova et al. (6 authors)

Journal of Clinical Oncology2016-05-203 citations

10.1200/jco.2016.34.15_suppl.e14101

Abstract A117: An integrated phosphoproteomic approach to dissect the mechanism of action of the novel dual PI3K/mTOR inhibitor PQR309 in B-cell lymphomas

Chiara Tarantelli, Eugenio Gaudio, Ivo Kwee, Luciano Cascione, Elena Bernasconi et al. (12 authors)

Molecular Cancer Therapeutics2015-12-01

10.1158/1535-7163.targ-15-a117

Abstract 2652: Pre-clinical activity and mechanism of action of the novel dual PI3K/mTOR inhibitor PQR309 in B-cell lymphomas

Chiara Tarantelli, Eugenio Gaudio, Ivo Kwee, Andrea Rinaldi, Elena Bernasconi et al. (20 authors)

Cancer Research2015-08-011 citations

10.1158/1538-7445.am2015-2652

A phase 1 first-in-human (FIH) dose-escalation (DE) study of the oral dual PI3K/mTOR inhibitor PQR309 in patients (pts) with advanced solid tumors: Final DE results.

Rebecca Kristeleit, Nicholas F. Brown, Dagmar Hess, Markus Joerger, Roger von Moos et al. (16 authors)

Journal of Clinical Oncology2015-05-203 citations

10.1200/jco.2015.33.15_suppl.2592

The Novel PI3K/mTOR Dual Inhibitor PQR309 in Pre-Clinical Lymphoma Models: Demonstration of Anti-Tumor Activity As Single Agent and in Combination and Identification of Gene Expression Signatures Associated with Response

Chiara Tarantelli, Eugenio Gaudio, Ivo Kwee, Andrea Rinaldi, Matteo Stifanelli et al. (19 authors)

Blood2014-12-062 citations

10.1182/blood.v124.21.1782.1782

Interventions

DRUGPQR309

Dosing will be orally, once a day for the duration of the trial.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Histologically or cytologically confirmed diagnosis of advanced solid tumor for which no therapy of proven efficacy is available. * Age ≥ 18 * Evidence of tumor progression with measurable or evaluable disease. * Use of adequate contraceptive measures for male patients. * Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1. * Signed informed consent.

Exclusion criteria

* Concomitant anticancer therapy (e.g., chemotherapy, radiotherapy, hormonal, immunotherapy, biological response modifier, signal transduction inhibitors) * Patients with a history of myocardial infarction or coronary artery bypass within the last 3 years. * Patients with severe/unstable angina, coronary/peripheral arterial bypass, symptomatic congestive heart failure NYHA Class 3 or 4, hypertension BP\>150/100mmHg. * Pre-diagnosed diabetes mellitus. * Fasting glucose \> 7.0 mmol/L or HbA1c \> 6%.

Design outcomes

Primary

Measure	Time frame
Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D)	In average 1 year

Secondary

Measure	Time frame	Description
To determine overall safety	1 year	Incidence of SAEs, incidence and severity of all AEs, changes of vital signs, physical examinations, body weight, changes of routine laboratory assessments.

Countries

Switzerland

Outcome results

None listed