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

Primary Purpose

Metastatic Breast Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PQR309
Eribulin
Sponsored by
PIQUR Therapeutics AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring TNBC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Universitarsi Vall d'Hebron
  • Insitut Català d´Oncologia
  • Fundación Instituto Valenciano de Oncología
  • Barts Cancer Institute
  • Churchill hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eribulin and PQR309

Arm Description

PQR309 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.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

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
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
Assessment of PQR309 and Eribulin blood concentration
Continous dosing and intermittent schedules of PQR309
Physical examination, Body weight in kg
Continous dosing and intermittent schedules
Physical examination, ECG
Continous dosing and intermittent schedules of PQR309
Vital signs like heart rate
Continous dosing and intermittent schedules of PQR309
Vital signs like blood pressure
Continous dosing and intermittent schedules of PQR309
Vital signs like body temperature
Continous dosing and intermittent schedules of PQR309
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 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
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
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 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
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
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
Intermittent schedule B: "Monday/ Thursday"
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
Intermittent schedule B: "Monday/ Thursday"
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
Intermittent schedule B: "Monday/ Thursday"
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞
Intermittent schedule B: "Monday/ Thursday"
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC(Racemate)
Intermittent schedule B: "Monday/ Thursday"
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
Intermittent schedule A: 2 days on/5 days off
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
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
Changes in Insulin levels
Continous dosing and intermittent schedules of PQR309
Changes of Routine laboratory -Haematology
Continous dosing and intermittent schedules of PQR309
Changes of Routine laboratory -blood chemistry
Continous dosing and intermittent schedules of PQR309
Changes of Routine laboratory -urinanalysis
Continous dosing and intermittent schedules of PQR309

Full Information

First Posted
December 21, 2015
Last Updated
March 20, 2019
Sponsor
PIQUR Therapeutics AG
Collaborators
Hospital Universitario Ramon y Cajal, Hospital Universitari Vall d'Hebron Research Institute, Institut Català d'Oncologia, Churchill Hospital, Barts Cancer Institute, Fundación Instituto Valenciano de Oncología
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1. Study Identification

Unique Protocol Identification Number
NCT02723877
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
March 28, 2016 (Actual)
Primary Completion Date
October 3, 2018 (Actual)
Study Completion Date
October 3, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PIQUR Therapeutics AG
Collaborators
Hospital Universitario Ramon y Cajal, Hospital Universitari Vall d'Hebron Research Institute, Institut Català d'Oncologia, Churchill Hospital, Barts Cancer Institute, Fundación Instituto Valenciano de Oncología

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
TNBC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eribulin and PQR309
Arm Type
Experimental
Arm Description
PQR309 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.
Intervention Type
Drug
Intervention Name(s)
PQR309
Intervention Description
Dual phosphatidylinositol 3-kinase phosphoinositide 3-kinase/ mammalian target of rapamycin Inhibitor (= PI3K/mTOR Inhibitor)
Intervention Type
Drug
Intervention Name(s)
Eribulin
Other Intervention Name(s)
eribulin mesylate, Halaven®
Intervention Description
non.taxane microtubule dynamics inhibitor
Primary Outcome Measure Information:
Title
Number of patients with treatment related Adverse Events and Serious Adverse Events as assessed by NCI CTCAEV4.03
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
Up to 6 months
Title
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)
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
Up to 15 months
Secondary Outcome Measure Information:
Title
Number of patients with Adverse Events and Serious Adverse Events and number of anormal laboratory values that constitute an Adverse Events on their own
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
Up to 12 months
Title
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.
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Assessment of PQR309 and Eribulin blood concentration
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Physical examination, Body weight in kg
Description
Continous dosing and intermittent schedules
Time Frame
up to 12 months
Title
Physical examination, ECG
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Vital signs like heart rate
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Vital signs like blood pressure
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Vital signs like body temperature
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Objective Response Rate (ORR), is defined as the best overall response (confirmed CR or PR) recorded for each patient since baseline.
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
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)
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
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.
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Progression- free survival (PFS) is defined as the time from study entry to progression or death due to any cause
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Time to treatment failure (TTF) is defined as the time from study entry to any treatment failure including disease progression or discontinuation of treatment
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
1-year survival, defined as the time from study entry to death as a result of any cause at 1-year cut-off date
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
up to 12 months
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC(Racemate)
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
Description
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.
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
Description
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.
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
Description
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.
Title
PK parameters of PQR309 and eribulin will include: AUC0-∞
Description
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.
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC
Description
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.
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞
Description
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 day on 1 and 8 and beyond cycle 1 on day 1
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: t1/2
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
Description
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
Title
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC (Racemate)
Description
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
Title
Changes in glucose levels
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
12 months
Title
Changes in Insulin levels
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
12 months
Title
Changes of Routine laboratory -Haematology
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
12 months
Title
Changes of Routine laboratory -blood chemistry
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
12 months
Title
Changes of Routine laboratory -urinanalysis
Description
Continous dosing and intermittent schedules of PQR309
Time Frame
12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Javier Cortes, PD Dr. med
Organizational Affiliation
Hospital Universitario Ramon y Cajal
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Universitarsi Vall d'Hebron
City
Barcelona
State/Province
Catalan
ZIP/Postal Code
08035
Country
Spain
Facility Name
Insitut Català d´Oncologia
City
Barcelona
Country
Spain
Facility Name
Fundación Instituto Valenciano de Oncología
City
Valencia
Country
Spain
Facility Name
Barts Cancer Institute
City
London
Country
United Kingdom
Facility Name
Churchill hospital
City
Oxford
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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