Clinical trial NCT02723877: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Keywords: TNBC
Lead sponsor: PIQUR Therapeutics AG
Sponsor class: INDUSTRY
Collaborators: name: Hospital Universitario Ramon y Cajal
name: Hospital Universitari Vall d'Hebron Research Institute
name: Institut Català d'Oncologia
name: Churchill Hospital
name: Barts Cancer Institute
name: Fundación Instituto Valenciano de Oncología
First posted: 2016-03-31
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of patients with treatment related Adverse Events and Serious Adverse Events as assessed by NCI CTCAEV4.03
timeFrame: Up to 6 months
measure: 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)
timeFrame: Up to 15 months
Secondary outcomes:
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
timeFrame: Up to 12 months
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.
timeFrame: up to 12 months
measure: Assessment of PQR309 and Eribulin blood concentration
timeFrame: up to 12 months
measure: Physical examination, Body weight in kg
timeFrame: up to 12 months
measure: Physical examination, ECG
timeFrame: up to 12 months
measure: Vital signs like heart rate
timeFrame: up to 12 months
measure: Vital signs like blood pressure
timeFrame: up to 12 months
measure: Vital signs like body temperature
timeFrame: up to 12 months
measure: Objective Response Rate (ORR), is defined as the best overall response (confirmed CR or PR) recorded for each patient since baseline.
timeFrame: up to 12 months
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)
timeFrame: up to 12 months
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.
timeFrame: up to 12 months
measure: Progression- free survival (PFS) is defined as the time from study entry to progression or death due to any cause
timeFrame: up to 12 months
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
timeFrame: up to 12 months
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
timeFrame: up to 12 months
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC(Racemate)
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
timeFrame: 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.
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
timeFrame: 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.
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
timeFrame: 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.
measure: PK parameters of PQR309 and eribulin will include: AUC0-∞
timeFrame: 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.
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC
timeFrame: 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.
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: t1/2
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax
timeFrame: 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
measure: Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC (Racemate)
timeFrame: 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
measure: Changes in glucose levels
timeFrame: 12 months
measure: Changes in Insulin levels
timeFrame: 12 months
measure: Changes of Routine laboratory -Haematology
timeFrame: 12 months
measure: Changes of Routine laboratory -blood chemistry
timeFrame: 12 months
measure: Changes of Routine laboratory -urinanalysis
timeFrame: 12 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Universitarsi Vall d'Hebron
state: Catalan
city: Barcelona
country: Spain
facility: Insitut Català d´Oncologia
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: London
country: United Kingdom
facility: Barts Cancer Institute
city: Oxford
country: United Kingdom
facility: Churchill hospital
Study officials:
affiliation: Hospital Universitario Ramon y Cajal
name: Javier Cortes, PD Dr. med
role: STUDY_DIRECTOR
References: