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

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

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).

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: PQR309; Drug: Eribulin

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Insitut Català d´Oncologia
  • Valencia, Spain
    • Fundación Instituto Valenciano de Oncología
  • Catalan
    • Barcelona, Catalan, Spain, 08035
      • Hospital Universitarsi Vall d'Hebron
• United Kingdom
  • London, United Kingdom
    • Barts Cancer Institute
  • Oxford, United Kingdom
    • Churchill Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eribulin and PQR309; 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.	Drug: PQR309; Dual phosphatidylinositol 3-kinase phosphoinositide 3-kinase/ mammalian target of rapamycin Inhibitor (= PI3K/mTOR Inhibitor); Drug: Eribulin; non.taxane microtubule dynamics inhibitor; Other Names: eribulin mesylate; Halaven®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Up to 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	up to 12 months
Assessment of PQR309 and Eribulin blood concentration	Continous dosing and intermittent schedules of PQR309	up to 12 months
Physical examination, Body weight in kg	Continous dosing and intermittent schedules	up to 12 months
Physical examination, ECG	Continous dosing and intermittent schedules of PQR309	up to 12 months
Vital signs like heart rate	Continous dosing and intermittent schedules of PQR309	up to 12 months
Vital signs like blood pressure	Continous dosing and intermittent schedules of PQR309	up to 12 months
Vital signs like body temperature	Continous dosing and intermittent schedules of PQR309	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	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	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	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	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	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	up to 12 months
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax	Intermittent schedule B: "Monday/ Thursday"	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"	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"	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"	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"	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	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	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: AUC0-24	Intermittent schedule A: 2 days on/5 days off	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.
PK parameters of PQR309 and eribulin will include: AUC0-∞	Intermittent schedule A: 2 days on/5 days off	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: RAC	Intermittent schedule A: 2 days on/5 days off	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: cmax	Continous Dosing	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	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-∞	Continous Dosing	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
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: t1/2	Continous Dosing	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: tmax	Continous Dosing	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: RAC (Racemate)	Continous Dosing	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
Changes in glucose levels	Continous dosing and intermittent schedules of PQR309	12 months
Changes in Insulin levels	Continous dosing and intermittent schedules of PQR309	12 months
Changes of Routine laboratory -Haematology	Continous dosing and intermittent schedules of PQR309	12 months
Changes of Routine laboratory -blood chemistry	Continous dosing and intermittent schedules of PQR309	12 months
Changes of Routine laboratory -urinanalysis	Continous dosing and intermittent schedules of PQR309	12 months

Collaborators and Investigators

• Sponsor: PIQUR Therapeutics AG
• Collaborators: Hospital Universitari Vall d'Hebron Research Institute; Institut Català d'Oncologia; Hospital Universitario Ramon y Cajal; Barts Cancer Institute; Fundación Instituto Valenciano de Oncología; Churchill Hospital
• Investigators: Study Director: Javier Cortes, PD Dr. med, Hospital Universitario Ramon y Cajal

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2016
• Primary Completion (Actual): October 3, 2018
• Study Completion (Actual): October 3, 2018

Study Registration Dates

• First Submitted: December 21, 2015
• First Submitted That Met QC Criteria: March 24, 2016
• First Posted (Estimate): March 31, 2016

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: TNBC
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: PQR309-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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