Description:
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).
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
PQR309-007
- NCT ID:
NCT02723877
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| PQR309 | | Eribulin and PQR309 |
| Eribulin | eribulin mesylate, Halaven® | Eribulin and PQR309 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Eribulin and PQR309 | Experimental | 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. | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of patients with treatment related Adverse Events and Serious Adverse Events as assessed by NCI CTCAEV4.03 |
| Time Frame: | Up to 6 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
Secondary Outcome Measures
| 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 |
| Time Frame: | Up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| 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. |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Assessment of PQR309 and Eribulin blood concentration |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Physical examination, Body weight in kg |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules |
| Measure: | Physical examination, ECG |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Vital signs like heart rate |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Vital signs like blood pressure |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Vital signs like body temperature |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Objective Response Rate (ORR), is defined as the best overall response (confirmed CR or PR) recorded for each patient since baseline. |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| 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) |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| 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. |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Progression- free survival (PFS) is defined as the time from study entry to progression or death due to any cause |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| 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 |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| 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 |
| Time Frame: | up to 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax |
| 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 |
| Safety Issue: | |
| Description: | Intermittent schedule B: "Monday/ Thursday" |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax |
| 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 |
| Safety Issue: | |
| Description: | Intermittent schedule B: "Monday/ Thursday" |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24 |
| 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 |
| Safety Issue: | |
| Description: | Intermittent schedule B: "Monday/ Thursday" |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞ |
| 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 |
| Safety Issue: | |
| Description: | Intermittent schedule B: "Monday/ Thursday" |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC(Racemate) |
| 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 |
| Safety Issue: | |
| Description: | Intermittent schedule B: "Monday/ Thursday" |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax |
| 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. |
| Safety Issue: | |
| Description: | Intermittent schedule A: 2 days on/5 days off |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax |
| 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. |
| Safety Issue: | |
| Description: | Intermittent schedule A: 2 days on/5 days off |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24 |
| 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. |
| Safety Issue: | |
| Description: | Intermittent schedule A: 2 days on/5 days off |
| Measure: | PK parameters of PQR309 and eribulin will include: AUC0-∞ |
| 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. |
| Safety Issue: | |
| Description: | Intermittent schedule A: 2 days on/5 days off |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC |
| 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. |
| Safety Issue: | |
| Description: | Intermittent schedule A: 2 days on/5 days off |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: cmax |
| 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 |
| Safety Issue: | |
| Description: | Continous Dosing |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-24 |
| 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 |
| Safety Issue: | |
| Description: | Continous Dosing |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: AUC0-∞ |
| 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 |
| Safety Issue: | |
| Description: | Continous Dosing |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: t1/2 |
| 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 |
| Safety Issue: | |
| Description: | Continous Dosing |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: tmax |
| 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 |
| Safety Issue: | |
| Description: | Continous Dosing |
| Measure: | Pharmacokinetic (PK) parameters of PQR309 and eribulin will include: RAC (Racemate) |
| 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 |
| Safety Issue: | |
| Description: | Continous Dosing |
| Measure: | Changes in glucose levels |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Changes in Insulin levels |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Changes of Routine laboratory -Haematology |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Changes of Routine laboratory -blood chemistry |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
| Measure: | Changes of Routine laboratory -urinanalysis |
| Time Frame: | 12 months |
| Safety Issue: | |
| Description: | Continous dosing and intermittent schedules of PQR309 |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | PIQUR Therapeutics AG |
Trial Keywords
Last Updated
March 22, 2019
