Clinical Trials /

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

NCT02723877

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PQR309 and Eribulin in Metastatic HER2 Negative and Triple-negative Breast Cancer (PIQHASSO)
  • Official Title: An Open Label, Non Randomized, Multicenter Phase 1/2b Study Investigating Safety and Efficacy of PQR309 and Eribulin Combination in Patients With Locally Advanced or Metastatic HER2 Negative and Triple-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: PQR309-007
  • NCT ID: NCT02723877

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
PQR309Eribulin and PQR309
Eribulineribulin mesylate, Halaven®Eribulin and PQR309

Purpose

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).

Detailed Description

      -  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.
    

Trial Arms

NameTypeDescriptionInterventions
Eribulin and PQR309ExperimentalPQR309 in combination with standard approved dose of eribulin mesylate 1.4 mg/m2 intravenous (iv) on days 1 and 8 in a period of 21 days per cycle will be investigated. . PQR309 will be administered maximum 15 minutes after eribulin iv dosing.
  • PQR309
  • Eribulin

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with treatment related Adverse Events and Serious Adverse Events as assessed by NCI CTCAEV4.03
Time Frame:Up to 6 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309

Secondary Outcome Measures

Measure:Number of patients with Adverse Events and Serious Adverse Events and number of anormal laboratory values that constitute an Adverse Events on their own
Time Frame:Up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure: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.
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Assessment of PQR309 and Eribulin blood concentration
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Physical examination, Body weight in kg
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules
Measure:Physical examination, ECG
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Vital signs like heart rate
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Vital signs like blood pressure
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Vital signs like body temperature
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Objective Response Rate (ORR), is defined as the best overall response (confirmed CR or PR) recorded for each patient since baseline.
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure: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)
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure: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.
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Progression- free survival (PFS) is defined as the time from study entry to progression or death due to any cause
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Time to treatment failure (TTF) is defined as the time from study entry to any treatment failure including disease progression or discontinuation of treatment
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:1-year survival, defined as the time from study entry to death as a result of any cause at 1-year cut-off date
Time Frame:up to 12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
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
Safety Issue:
Description:Intermittent schedule B: "Monday/ Thursday"
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
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
Safety Issue:
Description:Intermittent schedule B: "Monday/ Thursday"
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
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
Safety Issue:
Description:Intermittent schedule B: "Monday/ Thursday"
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞
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
Safety Issue:
Description:Intermittent schedule B: "Monday/ Thursday"
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC(Racemate)
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
Safety Issue:
Description:Intermittent schedule B: "Monday/ Thursday"
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
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.
Safety Issue:
Description:Intermittent schedule A: 2 days on/5 days off
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
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.
Safety Issue:
Description:Intermittent schedule A: 2 days on/5 days off
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
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.
Safety Issue:
Description:Intermittent schedule A: 2 days on/5 days off
Measure:PK parameters of PQR309 and eribulin will include: AUC0-∞
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.
Safety Issue:
Description:Intermittent schedule A: 2 days on/5 days off
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC
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.
Safety Issue:
Description:Intermittent schedule A: 2 days on/5 days off
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
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
Safety Issue:
Description:Continous Dosing
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
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
Safety Issue:
Description:Continous Dosing
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞
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 day on 1 and 8 and beyond cycle 1 on day 1
Safety Issue:
Description:Continous Dosing
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: t1/2
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
Safety Issue:
Description:Continous Dosing
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
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
Safety Issue:
Description:Continous Dosing
Measure:Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC (Racemate)
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
Safety Issue:
Description:Continous Dosing
Measure:Changes in glucose levels
Time Frame:12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Changes in Insulin levels
Time Frame:12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Changes of Routine laboratory -Haematology
Time Frame:12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Changes of Routine laboratory -blood chemistry
Time Frame:12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309
Measure:Changes of Routine laboratory -urinanalysis
Time Frame:12 months
Safety Issue:
Description:Continous dosing and intermittent schedules of PQR309

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PIQUR Therapeutics AG

Trial Keywords

  • TNBC

Last Updated

April 25, 2017