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A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors

NCT02162719

Description:

This multicenter, randomized, double-blind study will estimate the efficacy, safety and tolerability of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in participants with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC), as measured by progression-free survival (PFS) in all participants and in participants with phosphatase and tensin homolog (PTEN)-low tumors.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors
  • Official Title: A Randomized, Phase II, Multi-Center, Placebo-Controlled Study of Ipatasertib (GDC-0068), an Inhibitor of Akt, in Combination With Paclitaxel as Front-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: GO29227
  • SECONDARY ID: 2014-000469-35
  • NCT ID: NCT02162719

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
IpatasertibGDC-0068Ipatasertib + Paclitaxel
PaclitaxelIpatasertib + Paclitaxel
PlaceboPlacebo + Paclitaxel

Purpose

This multicenter, randomized, double-blind study will estimate the efficacy, safety and tolerability of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in participants with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC), as measured by progression-free survival (PFS) in all participants and in participants with phosphatase and tensin homolog (PTEN)-low tumors.

Trial Arms

NameTypeDescriptionInterventions
Ipatasertib + PaclitaxelExperimentalParticipants will receive ipatasertib and paclitaxel in cycles of 28 days (4 weeks) each and study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
  • Ipatasertib
  • Paclitaxel
Placebo + PaclitaxelPlacebo ComparatorParticipants will receive placebo and paclitaxel in cycles of 28 days (4 weeks) each and study treatment will continue until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
  • Paclitaxel
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented triple-negative adenocarcinoma of the breast that is
             inoperable locally advanced or metastatic and is not amenable to resection with
             curative intent

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor
             specimen, required prior to randomization

          -  Measurable disease, according to the RECIST v1.1

          -  Adequate hematologic and organ function within 14 days before the first study
             treatment

          -  For female participants of childbearing potential, agreement (by both participant and
             partner) to use an effective form of contraception for the duration of the study and
             for 6 months after last dose of study treatment

        Exclusion Criteria:

          -  Any previous therapy, including chemotherapy or hormonal or targeted therapy, for
             inoperable locally advanced or metastatic triple-negative adenocarcinoma of the
             breast. Participants may have received prior neoadjuvant or adjuvant chemotherapy
             and/or radiation treatment for locally advanced triple negative adenocarcinoma,
             provided all treatments were completed greater than or equal to (>/=) 6 months prior
             to Cycle 1 Day 1. Locally recurrent disease must not be amenable to resection with
             curative intent

          -  Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1

          -  Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor
             (ER) positive, or progesterone receptor (PR) positive breast cancer

          -  Previous therapy with Akt, PI3K, and/or mTOR inhibitors

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 30 days
             prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during
             the course of the study

          -  Known presence of the brain or spinal cord metastasis, as determined by computed
             tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or
             prior radiographic assessments
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS in All Participants, as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version (v) 1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline up to approximately 2.5 years
Safety Issue:
Description:
Measure:Steady State Area Under the Concentration Time Curve from Time Zero to 24 Hours (AUC0-24) of Ipatasertib
Time Frame:0.5-2 hours and 4-6 hours post-ipatasertib oral dose on Cycle 1 Day 1 (cycle length=28 days); 0-2 hours and 2-5 hours post-ipatasertib oral dose on Cycle 1 Day 8
Safety Issue:
Description:
Measure:Overall Survival (OS) in All Participants
Time Frame:Baseline up to death due to any cause (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:OS in Participants with PTEN-Low Tumors
Time Frame:Baseline up to death due to any cause (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:OS in Participants with Phosphoinositol 3 Kinase (PI3k)/Protein Kinase B (Akt) Pathway Activated Tumors
Time Frame:Baseline up to death due to any cause (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib
Time Frame:0.5-2 hours and 4-6 hours post-ipatasertib oral dose on Cycle 1 Day 1 (cycle length=28 days); 0-2 hours and 2-5 hours post-ipatasertib oral dose on Cycle 1 Day 8
Safety Issue:
Description:
Measure:European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Score
Time Frame:Day 1 of each 28-day cycle, at treatment completion/early discontinuation (up to approximately 2.5 years), at tumor follow-up and unscheduled adverse event follow-up (up to approximately 2.5 years overall)
Safety Issue:
Description:
Measure:Percentage of Participants With Protocol Defined Bothersome Treatment-Related Symptoms
Time Frame:Baseline up to approximately 2.5 years
Safety Issue:
Description:
Measure:Percentage of Participants with Confirmed Objective Tumor Response (Complete Response [CR] or Partial Response [PR]) in All Participants with Measurable Disease at Baseline, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Confirmed Objective Tumor Response (CR or PR) in Participants with Measurable Disease at Baseline and PTEN-Low Tumors, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Confirmed Objective Tumor Response (CR or PR) in All Participants with Measurable Disease at Baseline and PI3K/Akt Pathway Activated Tumors, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Duration of Confirmed Objective Response in Participants with Measurable Disease at Baseline, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Duration of Confirmed Objective Response in Participants with Measurable Disease at Baseline and PTEN-Low Tumors, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Duration of Confirmed Objective Response in Participants with Measurable Disease at Baseline and PI3K/Akt Pathway Activated Tumors, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Time to Disease Progression in Participants with Measurable Disease at Baseline, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Time to Disease Progression in Participants with Measurable Disease at Baseline and PTEN-Low Tumors, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:Time to Disease Progression in Participants with Measurable Disease at Baseline and PI3K/Akt Pathway Activated Tumors, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression (up to approximately 2.5 years)
Safety Issue:
Description:
Measure:PFS in All Participants with Measurable Disease at Baseline and PI3K/Akt Pathway Activated Tumors, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 2.5 years)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

November 3, 2017