Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02723877
Other study ID # PQR309-007
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
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
Health authority
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.

Study Design


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
See also
  Status Clinical Trial Phase
Withdrawn NCT04872608 - A Study of Letrozole, Palbociclib, and Onapristone ER in People With Metastatic Breast Cancer Phase 1
Terminated NCT02202746 - A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer Phase 2
Completed NCT02506556 - Phosphatidylinositol 3-kinase (PI3K) Alpha iNhibition In Advanced Breast Cancer Phase 2
Recruiting NCT05534438 - A Study on Adding Precisely Targeted Radiation Therapy (Stereotactic Body Radiation Therapy) to the Usual Treatment Approach (Drug Therapy) in People With Breast Cancer Phase 2
Recruiting NCT03368729 - Niraparib in Combination With Trastuzumab in Metastatic HER2+ Breast Cancer Phase 1/Phase 2
Completed NCT04103853 - Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer Phase 1
Terminated NCT01847599 - Educational Intervention to Adherence of Patients Treated by Capecitabine +/- Lapatinib N/A
Active, not recruiting NCT03147287 - Palbociclib After CDK and Endocrine Therapy (PACE) Phase 2
Not yet recruiting NCT06062498 - Elacestrant vs Elacestrant Plus a CDK4/6 Inhibitor in Patients With ERpositive/HER2-negative Advanced or Metastatic Breast Cancer Phase 2
Recruiting NCT05383196 - Onvansertib + Paclitaxel In TNBC Phase 1/Phase 2
Recruiting NCT04095390 - A Phase Ⅱ Trial of Pyrotinib Combination With CDK4/6 Inhibitor SHR6390 in Patients Prior Trastuzumab-treated Advanced HER2-Positive Breast Cancer Phase 2
Active, not recruiting NCT04432454 - Evaluation of Lasofoxifene Combined With Abemaciclib in Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation Phase 2
Recruiting NCT03323346 - Phase II Trial of Disulfiram With Copper in Metastatic Breast Cancer Phase 2
Recruiting NCT05744375 - Trastuzumab Deruxtecan in First-line HER2-positive Locally Advanced/MBC Patients Resistant to Trastuzumab+Pertuzumab Phase 2
Completed NCT02924883 - A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer (BC) Who Received Prior Trastuzumab and Taxane Based Therapy Phase 2
Completed NCT01942135 - Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3) Phase 3
Completed NCT01881230 - Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer) Phase 2/Phase 3
Active, not recruiting NCT04448886 - Sacituzumab Govitecan +/- Pembrolizumab In HR+ / HER2 - MBC Phase 2
Completed NCT01401959 - Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy Phase 2
Terminated NCT04720664 - Oral SM-88 in Patients With Metastatic HR+/HER2- Breast Cancer Phase 2