Back to resultsA 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
Primary Purpose
Breast Cancer, Non-small Lung Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Docetaxel
GDC-0032
Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer, Non-small Lung Cancer
Eligibility Criteria
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
Sites / Locations
- Florida Cancer Specialists - Tampa (Dr. MLK Blvd)
- Massachusetts General Hospital
- Dana Farber Cancer Institute
- Barbara Ann Karmanos Cancer Institute
- Sarah Cannon Research Institute
- Vanderbilt University Medical Center
- Texas Oncology, P.A; Baylor Sammons Cancer Center
- Texas Oncology, P.A. - Fort Worth
- Virginia Oncology Associates
- Yakima Valley Memorial Hospital/North Star Lodge
- UZ Leuven; Maag, -darm en leverziekten/endoscopie - Endoscopy
- Princess Margaret Hospital
- Hospital Universitari Vall d'Hebron
- Hospital Clinico Universitario de Valencia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm A: GDC-0032 + Docetaxel
Arm B: GDC-0032 + Paclitaxel
Arm C: GDC-0032 + Docetaxel
Arm D: GDC-0032 + Docetaxel
Arm E: GDC-0032 + Docetaxel
Arm F: GDC-0032 + Paclitaxel
Arm G: GDC-0032 + Paclitaxel
Arm Description
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.
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.
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Safety: Incidence of adverse events
Safety: Incidence of dose limiting toxicities
Secondary Outcome Measures
Area under the curve from time 0 to the last measurable concentration (AUC0-last)
Time to maximum observed plasma concentration (Tmax)
Maximum observed plasma concentration (Cmax)
Minimum observed plasma concentration (Cmin)
Objective response according to RECIST v1.1
Duration of response according to RECIST v1.1
Progression-free survival (PFS) according to RECIST v1.1
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01862081
Brief Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
July 16, 2013 (Actual)
Primary Completion Date
June 9, 2017 (Actual)
Study Completion Date
June 9, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Non-small Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: GDC-0032 + Docetaxel
Arm Type
Experimental
Arm Description
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 Title
Arm B: GDC-0032 + Paclitaxel
Arm Type
Experimental
Arm Description
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 Title
Arm C: GDC-0032 + Docetaxel
Arm Type
Experimental
Arm Description
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 Title
Arm D: GDC-0032 + Docetaxel
Arm Type
Experimental
Arm Description
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 Title
Arm E: GDC-0032 + Docetaxel
Arm Type
Experimental
Arm Description
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 Title
Arm F: GDC-0032 + Paclitaxel
Arm Type
Experimental
Arm Description
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 Title
Arm G: GDC-0032 + Paclitaxel
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
GDC-0032
Intervention Description
Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.
Primary Outcome Measure Information:
Title
Safety: Incidence of adverse events
Time Frame
Approximately 3 years
Title
Safety: Incidence of dose limiting toxicities
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Area under the curve from time 0 to the last measurable concentration (AUC0-last)
Time Frame
Up to 28 days
Title
Time to maximum observed plasma concentration (Tmax)
Time Frame
Up to 28 days
Title
Maximum observed plasma concentration (Cmax)
Time Frame
Up to 28 days
Title
Minimum observed plasma concentration (Cmin)
Time Frame
Up to 28 days
Title
Objective response according to RECIST v1.1
Time Frame
Approximately 3 years
Title
Duration of response according to RECIST v1.1
Time Frame
Approximately 3 years
Title
Progression-free survival (PFS) according to RECIST v1.1
Time Frame
Approximately 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Florida Cancer Specialists - Tampa (Dr. MLK Blvd)
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Oncology, P.A; Baylor Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Texas Oncology, P.A. - Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Yakima Valley Memorial Hospital/North Star Lodge
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States
Facility Name
UZ Leuven; Maag, -darm en leverziekten/endoscopie - Endoscopy
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4X 1K9
Country
Canada
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
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
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