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 - Full Text View

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 Intervention Model: Parallel Assignment Masking: Double Blind (Participant, 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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer

Drug Information available for: Paclitaxel

U.S. FDA Resources

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) ]
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) ]

Secondary Outcome Measures:

Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 2.5 years ]
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 ]
Overall Survival (OS) in All Participants [ Time Frame: Baseline up to death due to any cause (up to approximately 2.5 years) ]
OS in Participants with PTEN-Low Tumors [ Time Frame: Baseline up to death due to any cause (up to approximately 2.5 years) ]
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) ]
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 ]
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) ]
Percentage of Participants With Protocol Defined Bothersome Treatment-Related Symptoms [ Time Frame: Baseline up to approximately 2.5 years ]
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) ]
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) ]
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) ]
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) ]
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) ]
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) ]
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) ]
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) ]
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) ]
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) ]


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)
Sexes 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 ( EudraCT Number )
Study First Received:	June 11, 2014
Last Updated:	November 3, 2016

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 July 26, 2017