Clinical trial NCT01862081: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer, Non-small Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-24
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety: Incidence of adverse events
timeFrame: Approximately 3 years
measure: Safety: Incidence of dose limiting toxicities
timeFrame: Up to 28 days
Secondary outcomes:
measure: Area under the curve from time 0 to the last measurable concentration (AUC0-last)
timeFrame: Up to 28 days
measure: Time to maximum observed plasma concentration (Tmax)
timeFrame: Up to 28 days
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to 28 days
measure: Minimum observed plasma concentration (Cmin)
timeFrame: Up to 28 days
measure: Objective response according to RECIST v1.1
timeFrame: Approximately 3 years
measure: Duration of response according to RECIST v1.1
timeFrame: Approximately 3 years
measure: Progression-free survival (PFS) according to RECIST v1.1
timeFrame: Approximately 3 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Florida Cancer Specialists - Tampa (Dr. MLK Blvd)
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, P.A; Baylor Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. - Fort Worth
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Leuven
country: Belgium
facility: UZ Leuven; Maag, -darm en leverziekten/endoscopie - Endoscopy
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: