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Completed

NCT Number: NCT02723877

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

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).

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Key information

Conditions

Metastatic Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Hospital Universitarsi Vall d'Hebron, Barcelona, Catalan, Spain

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About this study

  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PQR309

Drug

Dual phosphatidylinositol 3-kinase phosphoinositide 3-kinase/ mammalian target of rapamycin Inhibitor (= PI3K/mTOR Inhibitor)

Eribulin

Drug

non.taxane microtubule dynamics inhibitor

Other names: eribulin mesylate, Halaven®

Primary outcomes

  1. Number of patients with treatment related Adverse Events and Serious Adverse Events as assessed by NCI CTCAEV4.03

    Time frame: Up to 6 months

    Continous dosing and intermittent schedules of PQR309

  2. 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)

    Time frame: Up to 15 months

    Continous dosing and intermittent schedules of PQR309

Secondary outcomes

  1. 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

    Continous dosing and intermittent schedules of PQR309

  2. 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

    Continous dosing and intermittent schedules of PQR309

  3. Assessment of PQR309 and Eribulin blood concentration

    Time frame: up to 12 months

    Continous dosing and intermittent schedules of PQR309

  4. Physical examination, Body weight in kg

    Time frame: up to 12 months

    Continous dosing and intermittent schedules

  5. Physical examination, ECG

    Time frame: up to 12 months

    Continous dosing and intermittent schedules of PQR309

  6. Vital signs like heart rate

    Time frame: up to 12 months

    Continous dosing and intermittent schedules of PQR309

  7. Vital signs like blood pressure

    Time frame: up to 12 months

    Continous dosing and intermittent schedules of PQR309

  8. Vital signs like body temperature

    Time frame: up to 12 months

    Continous dosing and intermittent schedules of PQR309

  9. 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

    Continous dosing and intermittent schedules of PQR309

  10. 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

    Continous dosing and intermittent schedules of PQR309

  11. 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

    Continous dosing and intermittent schedules of PQR309

  12. 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

    Continous dosing and intermittent schedules of PQR309

  13. 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

    Continous dosing and intermittent schedules of PQR309

  14. 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

    Continous dosing and intermittent schedules of PQR309

  15. 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

    Intermittent schedule B: "Monday/ Thursday"

  16. 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

    Intermittent schedule B: "Monday/ Thursday"

  17. 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

    Intermittent schedule B: "Monday/ Thursday"

  18. 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

    Intermittent schedule B: "Monday/ Thursday"

  19. 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

    Intermittent schedule B: "Monday/ Thursday"

  20. 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.

    Intermittent schedule A: 2 days on/5 days off

  21. 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.

    Intermittent schedule A: 2 days on/5 days off

  22. 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.

    Intermittent schedule A: 2 days on/5 days off

  23. 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.

    Intermittent schedule A: 2 days on/5 days off

  24. 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.

    Intermittent schedule A: 2 days on/5 days off

  25. 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

    Continous Dosing

  26. 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

    Continous Dosing

  27. 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

    Continous Dosing

  28. 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

    Continous Dosing

  29. 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

    Continous Dosing

  30. 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

    Continous Dosing

  31. Changes in glucose levels

    Time frame: 12 months

    Continous dosing and intermittent schedules of PQR309

  32. Changes in Insulin levels

    Time frame: 12 months

    Continous dosing and intermittent schedules of PQR309

  33. Changes of Routine laboratory -Haematology

    Time frame: 12 months

    Continous dosing and intermittent schedules of PQR309

  34. Changes of Routine laboratory -blood chemistry

    Time frame: 12 months

    Continous dosing and intermittent schedules of PQR309

  35. Changes of Routine laboratory -urinanalysis

    Time frame: 12 months

    Continous dosing and intermittent schedules of PQR309

Sponsors and collaborators

Lead sponsor

PIQUR Therapeutics AG

Industry

Collaborators

  • 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

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Mar 31, 2016
Registry last updated
Mar 22, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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