PQR309 and Eribulin in Metastatic HER2 Negative and Triple-negative Breast Cancer (PIQHASSO)

PIQUR Therapeutics AG41 enrolled

Overview

This study is an open-label,non randomized, multi-center, phase 1/2b (dose escalation followed by expansion part) study evaluating clinical safety, efficacy and pharmacokinetics of PQR309 in combination with standard dose of eribulin in patients with locally advanced or metastatic HER2-negative (escalation part) and Triple Negative Breast Cancer (expansion part).

* The primary objective of the escalation part is to assess the maximum tolerated dose (MTD) of PQR309 combined with the standard eribulin dose in patients with HER2 negative breast cancer following a "modified" 3 by 3 design. * For the expansion part the objective is to evaluate efficacy of PQR309 in combination with eribulin in patients with Triple Negative Breast Cancer * Once the MTD of continuous daily PQR309 dosing has been established, intermittent schedules of PQR309 ("2 days on/ 5 days off" or "Monday / Thursday") will be evaluated.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Breast Cancer

Interventions

PQR309DRUG

Dual phosphatidylinositol 3-kinase phosphoinositide 3-kinase/ mammalian target of rapamycin Inhibitor (= PI3K/mTOR Inhibitor)

EribulinDRUG

non.taxane microtubule dynamics inhibitor

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically/cytologically confirmed diagnosis of breast cancer. Radiological evidence of inoperable locally advanced or metastatic breast cancer. * HER2 negative breast cancer (based on the most recent analyzed biopsy) defined as a negative in situ hybridization test or an immunohistochemistry status of 0, 1+ or 2+. * Received at least 2 and no more than 5 prio chemotherapeutic regimens in locally advanced and/or metastatic setting. * Prior therapy has to include an anthracycline and a taxane in any combination or order. * For Expansion part: Triple-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0,1+ or 2+ER abnd PR status \<10% by local laboratory testing. Exclusion Criteria: * Previous systemic treatment with PI3K,mTOR or AKT inhibitors (allowed in the escalation part). * Previous treatment with eribulin (allowed in the escalation part). Known hypersensitivity to any of the excipients of PQR309 or eribulin.Concurrent treatment with other approved or investigational antineoplastic agent. * Symptomatic Central Nervous System metastases. The patient must have completed any prior local treatment for CNS metastases \> 28 days prior to first dose of the study drug (including radiotherapy and/or surgery). * Clinically manifested diabetes mellitus(treated and/or clinical signs with fasting glucose \>125mg/dl or HbA1c\>7%), or documented steroid induced diabetes mellitus.

Locations (5)

Hospital Universitarsi Vall d'Hebron

Barcelona, Catalan, Spain

Insitut Català d´Oncologia

Barcelona, Spain

Fundación Instituto Valenciano de Oncología

Valencia, Spain

Barts Cancer Institute

London, United Kingdom

Outcomes

Primary Outcomes

Number of patients with treatment related Adverse Events and Serious Adverse Events as assessed by NCI CTCAEV4.03

Continous dosing and intermittent schedules of PQR309

Time frame: Up to 6 months

RECIST the Response criteria for solid tumors will be used to identify clinical benefit rate (CBR) including complete Response (CR), partial Response (PR) and stable disease (SD)

Continous dosing and intermittent schedules of PQR309

Time frame: Up to 15 months

Secondary Outcomes

Number of patients with Adverse Events and Serious Adverse Events and number of anormal laboratory values that constitute an Adverse Events on their own

Continous dosing and intermittent schedules of PQR309

Time frame: Up to 12 months

Number and percent of patients having each ECOG (Eastern Oncology Cooperative Group) performance status level will be presented for baseline and each post-baseline measurement.

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Assessment of PQR309 and Eribulin blood concentration

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Physical examination, Body weight in kg

Continous dosing and intermittent schedules

Time frame: up to 12 months

Physical examination, ECG

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Data from ClinicalTrials.gov

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Oxford, United Kingdom

Vital signs like heart rate

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Vital signs like blood pressure

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Vital signs like body temperature

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Objective Response Rate (ORR), is defined as the best overall response (confirmed CR or PR) recorded for each patient since baseline.

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Time to Response (TTR) is defined, for patients with tumor response, as the time from the date of study entry to the first documentation of response (complete or partial)

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Duration of response (DOR) is defined, for the patients with tumor response, as the time from the date of the first confirmed response to disease progression.

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Progression- free survival (PFS) is defined as the time from study entry to progression or death due to any cause

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Time to treatment failure (TTF) is defined as the time from study entry to any treatment failure including disease progression or discontinuation of treatment

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

1-year survival, defined as the time from study entry to death as a result of any cause at 1-year cut-off date

Continous dosing and intermittent schedules of PQR309

Time frame: up to 12 months

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax

Intermittent schedule B: "Monday/ Thursday"

Time frame: On Cycle 1 Day 8: pre-dose, end of eribulin infusion, 2h and 6h post end of eribulin infusion and on Day 15: pre-dose and one sample between 1 and 3 hours post PQR309 dose

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax

Intermittent schedule B: "Monday/ Thursday"

Time frame: On Cycle 1 Day 8: pre-dose, end of eribulin infusion, 2h and 6h post end of eribulin infusion and on Day 15: pre-dose and one sample between 1 and 3 hours post PQR309 dose

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24

Intermittent schedule B: "Monday/ Thursday"

Time frame: On Cycle 1 Day 8: pre-dose, end of eribulin infusion, 2h and 6h post end of eribulin infusion and on Day 15: pre-dose and one sample between 1 and 3 hours post PQR309 dose

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞

Intermittent schedule B: "Monday/ Thursday"

Time frame: On Cycle 1 Day 8: pre-dose, end of eribulin infusion, 2h and 6h post end of eribulin infusion and on Day 15: pre-dose and one sample between 1 and 3 hours post PQR309 dose

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC(Racemate)

Intermittent schedule B: "Monday/ Thursday"

Time frame: On Cycle 1 Day 8: pre-dose, end of eribulin infusion, 2h and 6h post end of eribulin infusion and on Day 15: pre-dose and one sample between 1 and 3 hours post PQR309 dose

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax

Intermittent schedule A: 2 days on/5 days off

Time frame: PK is being assessed during Cycle 1 on Day 8: pre-dose, end of eribulin infusion, 2h and 6h post end of eribulin infusion. On Cycle 1 Day 15: pre-dose and one sample between 1 and 3 hours post PQR309 dose.

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax

Intermittent schedule A: 2 days on/5 days off

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24

Intermittent schedule A: 2 days on/5 days off

PK parameters of PQR309 and eribulin will include: AUC0-∞

Intermittent schedule A: 2 days on/5 days off

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC

Intermittent schedule A: 2 days on/5 days off

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax

Continous Dosing

Time frame: It will be measured pre-dose and at the end of eribulin infusion and 0.5h, 1h, 2h, 4h, and 8h post end and at end of eribulin infusion and 0.5h, 1h, 2h, 4h, and 8h post end of eribulin during Cycle 1 on day 1 and 8 and beyond cycle 1 on day 1

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24

Continous Dosing

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞

Continous Dosing

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: t1/2

Continous Dosing

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax

Continous Dosing

Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC (Racemate)

Continous Dosing

Changes in glucose levels

Continous dosing and intermittent schedules of PQR309

Time frame: 12 months

Changes in Insulin levels

Continous dosing and intermittent schedules of PQR309

Time frame: 12 months

Changes of Routine laboratory -Haematology

Continous dosing and intermittent schedules of PQR309

Time frame: 12 months

Changes of Routine laboratory -blood chemistry

Continous dosing and intermittent schedules of PQR309

Time frame: 12 months

Changes of Routine laboratory -urinanalysis

Continous dosing and intermittent schedules of PQR309

Time frame: 12 months