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Trial record 5 of 9 for:    PIQUR

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

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ClinicalTrials.gov Identifier: NCT02723877
Recruitment Status : Completed
First Posted : March 31, 2016
Last Update Posted : October 19, 2018
Sponsor:
Collaborators:
Hospital Universitario Ramon y Cajal
Hospital Universitari Vall d'Hebron Research Institute
Institut Català d'Oncologia
Churchill Hospital
Barts Cancer Institute
Fundación Instituto Valenciano de Oncología
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: PQR309 Drug: Eribulin Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 28, 2016
Actual Primary Completion Date : October 3, 2018
Actual Study Completion Date : October 3, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Eribulin and 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.
Drug: PQR309
Dual phosphatidylinositol 3-kinase phosphoinositide 3-kinase/ mammalian target of rapamycin Inhibitor (= PI3K/mTOR Inhibitor)

Drug: Eribulin
non.taxane microtubule dynamics inhibitor
Other Names:
  • eribulin mesylate
  • Halaven®




Primary Outcome Measures :
  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 Outcome Measures :
  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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02723877


Locations
Spain
Hospital Universitarsi Vall d'Hebron
Barcelona, Catalan, Spain, 08035
Insitut Català d´Oncologia
Barcelona, Spain
Fundación Instituto Valenciano de Oncología
Valencia, Spain
United Kingdom
Barts Cancer Institute
London, United Kingdom
Churchill hospital
Oxford, United Kingdom
Sponsors and Collaborators
PIQUR Therapeutics AG
Hospital Universitario Ramon y Cajal
Hospital Universitari Vall d'Hebron Research Institute
Institut Català d'Oncologia
Churchill Hospital
Barts Cancer Institute
Fundación Instituto Valenciano de Oncología
Investigators
Study Director: Javier Cortes, PD Dr. med Hospital Universitario Ramon y Cajal

Responsible Party: PIQUR Therapeutics AG
ClinicalTrials.gov Identifier: NCT02723877     History of Changes
Other Study ID Numbers: PQR309-007
First Posted: March 31, 2016    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by PIQUR Therapeutics AG:
TNBC

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases