Phase 2
Completed N=124
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
Source: ClinicalTrials.gov NCT02162719 ↗Enrolled (actual)
124
Serious AEs
24.4%
Results posted
Jan 2021
Primary outcomePrimary: Progression Free Survival (PFS) — 6.18; 4.93 Months — p=0.0372
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) |
6.18; 4.93 | 0.0372 sig |
| PRIMARY PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors |
6.18; 3.65 | 0.1753 |
| SECONDARY PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors |
9.03; 4.93 | 0.3636 |
| SECONDARY Overall Survival (OS) |
25.8; 16.9 | 0.3607 |
| SECONDARY OS in Participants With PTEN-Low Tumors |
23.1; 15.8 | 0.4422 |
| SECONDARY OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
25.8; 22.1 | 0.7599 |
| SECONDARY Objective Response Rate (ORR) |
40.3; 32.3 | — |
| SECONDARY ORR in Participants With PTEN-Low Tumors |
48.0; 26.1 | — |
| SECONDARY ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
50.0; 43.8 | — |
| SECONDARY Duration of Response |
7.85; 7.43 | — |
| SECONDARY Duration of Response in Participants With PTEN-Low Tumors |
6.54; 7.49 | — |
| SECONDARY Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
11.24; 6.06 | — |
| SECONDARY Time to Disease Progression |
6.18; 4.96 | — |
| SECONDARY Time to Disease Progression in Participants With PTEN-Low Tumors |
6.18; 3.94 | — |
| SECONDARY Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors |
9.03; 4.93 | — |
| SECONDARY Safety: Percentage of Participants With Adverse Events |
100.0; 96.8 | — |
| SECONDARY Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib |
NA | — |
| SECONDARY Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib |
NA | — |
| SECONDARY Patient Reported Outcome (PRO) Measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) Score |
7.60; -0.63; 9.42; -3.88; 5.44; -4.17 | — |
| SECONDARY PRO Measure: Percentage of Participants With Improved, Worsened, or Remained Stable for Bothersome Side Effects of Treatment Measured by the Scales of the EORTC QLQ-C30 |
10.5; 18.9; 64.9; 66.0; 24.6; 15.1 | — |
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
Data sourced from ClinicalTrials.gov (NCT02162719). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.