PQR309 and Eribulin in Metastatic HER2 Negative and Triple-negative Breast Cancer (PIQHASSO)
- Registration Number
- NCT02723877
- Lead Sponsor
- PIQUR Therapeutics AG
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 41
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Eribulin and PQR309 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. Eribulin and PQR309 Eribulin 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.
- Primary Outcome Measures
Name Time Method Number of patients with treatment related Adverse Events and Serious Adverse Events as assessed by NCI CTCAEV4.03 Up to 6 months 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) Up to 15 months Continous dosing and intermittent schedules of PQR309
- Secondary Outcome Measures
Name Time Method Physical examination, Body weight in kg up to 12 months Continous dosing and intermittent schedules
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. up to 12 months Continous dosing and intermittent schedules of PQR309
PK parameters of PQR309 and eribulin will include: AUC0-∞ 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. Intermittent schedule A: 2 days on/5 days off
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC 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. Intermittent schedule A: 2 days on/5 days off
Changes in Insulin levels 12 months Continous dosing and intermittent schedules of PQR309
Assessment of PQR309 and Eribulin blood concentration up to 12 months 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. up to 12 months 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 up to 12 months Continous dosing and intermittent schedules of PQR309
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax 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 Continous Dosing
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax 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 Continous Dosing
Physical examination, ECG up to 12 months Continous dosing and intermittent schedules of PQR309
Number of patients with Adverse Events and Serious Adverse Events and number of anormal laboratory values that constitute an Adverse Events on their own Up to 12 months Continous dosing and intermittent schedules of PQR309
Vital signs like body temperature up to 12 months 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) up to 12 months 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 up to 12 months Continous dosing and intermittent schedules of PQR309
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞ 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 Continous Dosing
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: t1/2 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 Continous Dosing
Changes of Routine laboratory -Haematology 12 months Continous dosing and intermittent schedules of PQR309
Changes of Routine laboratory -urinanalysis 12 months Continous dosing and intermittent schedules of PQR309
Vital signs like heart rate up to 12 months Continous dosing and intermittent schedules of PQR309
Vital signs like blood pressure up to 12 months Continous dosing and intermittent schedules of PQR309
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24 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 Continous Dosing
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC(Racemate) 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 Intermittent schedule B: "Monday/ Thursday"
Changes of Routine laboratory -blood chemistry 12 months 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. up to 12 months 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 up to 12 months Continous dosing and intermittent schedules of PQR309
Changes in glucose levels 12 months Continous dosing and intermittent schedules of PQR309
Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC (Racemate) 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 Continous Dosing
Trial Locations
- Locations (5)
Churchill hospital
🇬🇧Oxford, United Kingdom
Insitut Català d´Oncologia
🇪🇸Barcelona, Spain
Barts Cancer Institute
🇬🇧London, United Kingdom
Fundación Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Hospital Universitarsi Vall d'Hebron
🇪🇸Barcelona, Catalan, Spain