Breast Cancer, Non-small Lung Cancer
Conditions
Brief summary
This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral GDC-0032 administered in combination with either docetaxel or with paclitaxel. Patients treated with the GDC-0032 and docetaxel have HER2-negative locally recurrent or metastatic breast cancer or non-small cell lung cancer (NSCLC). Patients treated with the GDC-0032 and paclitaxel combination have human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer. There are two potential stages within each arm of this study: a dose-escalation stage (Stage 1) and a dose-expansion stage (Stage 2). Once the maximum tolerated dose of GDC-0032 in a given arm has been established from dose escalation, additional patients with each combination will be enrolled in Stage 2.
Interventions
DRUGDocetaxel
Participants will receive docetaxel 75 milligrams per meter-squared (mg/m\^2) intravenous (IV) dose on Day 1 of each 21-day cycle.
DRUGGDC-0032
Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.
DRUGPaclitaxel
Participants will receive paclitaxel 80 mg/m\^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>=18 years * For paclitaxel combination arms: histologically or cytologically documented adenocarcinoma of the breast with locally recurrent or metastatic disease * For docetaxel combination arms: histologically or cytologically documented adenocarcinoma of the breast with locally recurrent or metastatic disease or histologically documented advanced (Stage IV) or recurrent NSCLC * For participants with breast cancer: HER2-negative disease as defined by local clinical guidelines * Participants with NSCLC to be treated with docetaxel need to have received at least one prior anti-cancer treatment regimen in an advanced setting and to have docetaxel be considered appropriate treatment * Evaluable or measurable disease per response evaluation criteria in solid tumors (RECIST) v.1.1 * Life expectancy \>=12 weeks * Eastern cooperative oncology group (ECOG) performance status of 0 or 1 at screening * Adequate hematologic and end organ function * Use of highly effective form of contraception
Exclusion criteria
* Prior anti-cancer therapy * Prior treatment with phosphoinositide 3-kinase (PI3K) inhibitor * Known significant hypersensitivity to any components of study treatment * Grade \>=2 peripheral neuropathy * Type 1 or Type 2 diabetes * Grade \>=2 hypercholesterolemia or hypertriglyceridemia * Congenital long QT syndrome * Active congestive heart failure or ventricular arrhythmia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Incidence of adverse events | Approximately 3 years |
| Safety: Incidence of dose limiting toxicities | Up to 28 days |
Secondary
| Measure | Time frame |
|---|---|
| Maximum observed plasma concentration (Cmax) | Up to 28 days |
| Minimum observed plasma concentration (Cmin) | Up to 28 days |
| Area under the curve from time 0 to the last measurable concentration (AUC0-last) | Up to 28 days |
| Duration of response according to RECIST v1.1 | Approximately 3 years |
| Progression-free survival (PFS) according to RECIST v1.1 | Approximately 3 years |
| Objective response according to RECIST v1.1 | Approximately 3 years |
| Time to maximum observed plasma concentration (Tmax) | Up to 28 days |
Countries
Belgium, Canada, Spain, United States
Outcome results
None listed