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

Metastatic Breast Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02723877
• Other study ID #: PQR309-007
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 28, 2016
• Est. completion date: October 3, 2018

Study information

• Verified date: March 2019
• Source: PIQUR Therapeutics AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: October 3, 2018
• Est. primary completion date: October 3, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• PQR309
Dual phosphatidylinositol 3-kinase phosphoinositide 3-kinase/ mammalian target of rapamycin Inhibitor (= PI3K/mTOR Inhibitor)
• Eribulin
non.taxane microtubule dynamics inhibitor

Locations

Country	Name	City	State
Spain	Hospital Universitarsi Vall d'Hebron	Barcelona	Catalan
Spain	Insitut Català d´Oncologia	Barcelona
Spain	Fundación Instituto Valenciano de Oncología	Valencia
United Kingdom	Barts Cancer Institute	London
United Kingdom	Churchill hospital	Oxford

Sponsors (7)

Lead Sponsor	Collaborator
PIQUR Therapeutics AG	Barts Cancer Institute, Churchill Hospital, Fundación Instituto Valenciano de Oncología, Hospital Universitari Vall d'Hebron Research Institute, Hospital Universitario Ramon y Cajal, Institut Català d'Oncologia

Countries where clinical trial is conducted

Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Assessment of PQR309 and Eribulin blood concentration	Continous dosing and intermittent schedules of PQR309	up to 12 months
Secondary	Physical examination, Body weight in kg	Continous dosing and intermittent schedules	up to 12 months
Secondary	Physical examination, ECG	Continous dosing and intermittent schedules of PQR309	up to 12 months
Secondary	Vital signs like heart rate	Continous dosing and intermittent schedules of PQR309	up to 12 months
Secondary	Vital signs like blood pressure	Continous dosing and intermittent schedules of PQR309	up to 12 months
Secondary	Vital signs like body temperature	Continous dosing and intermittent schedules of PQR309	up to 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-8	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	PK parameters of PQR309 and eribulin will include: AUC0-8	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-8	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes in glucose levels	Continous dosing and intermittent schedules of PQR309	12 months
Secondary	Changes in Insulin levels	Continous dosing and intermittent schedules of PQR309	12 months
Secondary	Changes of Routine laboratory -Haematology	Continous dosing and intermittent schedules of PQR309	12 months
Secondary	Changes of Routine laboratory -blood chemistry	Continous dosing and intermittent schedules of PQR309	12 months
Secondary	Changes of Routine laboratory -urinanalysis	Continous dosing and intermittent schedules of PQR309	12 months