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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT02162719
First received: June 11, 2014
Last updated: November 3, 2016
Last verified: November 2016
  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.

Condition Intervention Phase
Breast Neoplasms
Drug: Ipatasertib
Drug: Paclitaxel
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • PFS in Participants with 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 2.5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall Survival (OS) in All Participants [ Time Frame: Baseline up to death due to any cause (up to approximately 2.5 years) ] [ Designated as safety issue: No ]
  • OS in Participants with PTEN-Low Tumors [ Time Frame: Baseline up to death due to any cause (up to approximately 2.5 years) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Protocol Defined Bothersome Treatment-Related Symptoms [ Time Frame: Baseline up to approximately 2.5 years ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 124
Study Start Date: September 2014
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipatasertib + Paclitaxel
Participants 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.
Drug: Ipatasertib
Participants will receive ipatasertib orally 400 milligrams (mg) daily on Days 1-21 of each 28-day cycle.
Other Name: GDC-0068
Drug: Paclitaxel
Participants will receive paclitaxel 80 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1, 8, and 15 of each cycle.
Placebo Comparator: Placebo + Paclitaxel
Participants 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.
Drug: Paclitaxel
Participants will receive paclitaxel 80 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1, 8, and 15 of each cycle.
Drug: Placebo
Participants will receive oral placebo matched to ipatasertib, daily on Days 1-21 of each 28-day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02162719

  Show 63 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02162719     History of Changes
Other Study ID Numbers: GO29227  2014-000469-35 
Study First Received: June 11, 2014
Last Updated: November 3, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016