A Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of GDC-0032 in Combination With Docetaxel or With Paclitaxel in Patients With HER2-negative Locally Recurrent or Metastatic Breast Cancer or Non-small Cell Lung Cancer
- Conditions
- Breast Cancer, Non-small Lung Cancer
- Interventions
- Registration Number
- NCT01862081
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: GDC-0032 + Docetaxel GDC-0032 Participants will receive GDC-0032 once daily for 21 consecutive days (beginning from Day 1) in each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm C: GDC-0032 + Docetaxel GDC-0032 Participants will receive GDC-0032 once daily on Day 1 and Days 8-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm E: GDC-0032 + Docetaxel GDC-0032 Participants will receive GDC-0032 once daily on Days 1-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm F: GDC-0032 + Paclitaxel GDC-0032 Participants will receive GDC-0032 once daily on a 5-days on, 2-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle. Arm B: GDC-0032 + Paclitaxel GDC-0032 Participants will receive GDC-0032 once daily for 28 consecutive days (beginning from Day 1) in each 28-day cycle along with Paclitaxel on Days 1, 8, 15 and 22 of each 28-day cycle. Arm D: GDC-0032 + Docetaxel GDC-0032 Participants will receive GDC-0032 once daily on Days 2-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm G: GDC-0032 + Paclitaxel GDC-0032 Participants will receive GDC-0032 once daily on a 3-days on, 4-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle. Arm A: GDC-0032 + Docetaxel Docetaxel Participants will receive GDC-0032 once daily for 21 consecutive days (beginning from Day 1) in each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm E: GDC-0032 + Docetaxel Docetaxel Participants will receive GDC-0032 once daily on Days 1-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm C: GDC-0032 + Docetaxel Docetaxel Participants will receive GDC-0032 once daily on Day 1 and Days 8-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm B: GDC-0032 + Paclitaxel Paclitaxel Participants will receive GDC-0032 once daily for 28 consecutive days (beginning from Day 1) in each 28-day cycle along with Paclitaxel on Days 1, 8, 15 and 22 of each 28-day cycle. Arm D: GDC-0032 + Docetaxel Docetaxel Participants will receive GDC-0032 once daily on Days 2-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle. Arm F: GDC-0032 + Paclitaxel Paclitaxel Participants will receive GDC-0032 once daily on a 5-days on, 2-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle. Arm G: GDC-0032 + Paclitaxel Paclitaxel Participants will receive GDC-0032 once daily on a 3-days on, 4-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle.
- Primary Outcome Measures
Name Time Method Safety: Incidence of adverse events Approximately 3 years Safety: Incidence of dose limiting toxicities Up to 28 days
- Secondary Outcome Measures
Name Time Method Time to maximum observed plasma concentration (Tmax) Up to 28 days Area under the curve from time 0 to the last measurable concentration (AUC0-last) Up to 28 days Maximum observed plasma concentration (Cmax) Up to 28 days Minimum observed plasma concentration (Cmin) Up to 28 days Objective response according to RECIST v1.1 Approximately 3 years Duration of response according to RECIST v1.1 Approximately 3 years Progression-free survival (PFS) according to RECIST v1.1 Approximately 3 years
Trial Locations
- Locations (14)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Texas Oncology, P.A; Baylor Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Yakima Valley Memorial Hospital/North Star Lodge
🇺🇸Yakima, Washington, United States
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Florida Cancer Specialists - Tampa (Dr. MLK Blvd)
🇺🇸Tampa, Florida, United States
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Texas Oncology, P.A. - Fort Worth
🇺🇸Fort Worth, Texas, United States
UZ Leuven; Maag, -darm en leverziekten/endoscopie - Endoscopy
🇧🇪Leuven, Belgium