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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer, Non-small Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: GDC-0032; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven; Maag, -darm en leverziekten/endoscopie - Endoscopy
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4X 1K9
      • Princess Margaret Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
• United States
  • Florida
    • Tampa, Florida, United States, 33607
      • Florida Cancer Specialists - Tampa (Dr. MLK Blvd)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Oncology, P.A; Baylor Sammons Cancer Center
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, P.A. - Fort Worth
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital/North Star Lodge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: GDC-0032 + 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.	Drug: Docetaxel; Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.; Drug: GDC-0032; Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.
Experimental: Arm B: GDC-0032 + 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.	Drug: GDC-0032; Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.; Drug: Paclitaxel; Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.
Experimental: Arm C: GDC-0032 + 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.	Drug: Docetaxel; Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.; Drug: GDC-0032; Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.
Experimental: Arm D: GDC-0032 + 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.	Drug: Docetaxel; Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.; Drug: GDC-0032; Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.
Experimental: Arm E: GDC-0032 + 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.	Drug: Docetaxel; Participants will receive docetaxel 75 milligrams per meter-squared (mg/m^2) intravenous (IV) dose on Day 1 of each 21-day cycle.; Drug: GDC-0032; Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.
Experimental: Arm F: GDC-0032 + 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.	Drug: GDC-0032; Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.; Drug: Paclitaxel; Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.
Experimental: Arm G: GDC-0032 + 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.	Drug: GDC-0032; Participants will receive escalated dose of GDC-0032. The initial dose will be 3 mg capsules or 2 mg tablets.; Drug: Paclitaxel; Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	Approximately 3 years
Safety: Incidence of dose limiting toxicities	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration (Cmax)	Up to 28 days
Area under the curve from time 0 to the last measurable concentration (AUC0-last)	Up to 28 days
Time to maximum observed plasma concentration (Tmax)	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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2013
• Primary Completion (Actual): June 9, 2017
• Study Completion (Actual): June 9, 2017

Study Registration Dates

• First Submitted: May 22, 2013
• First Submitted That Met QC Criteria: May 22, 2013
• First Posted (Estimate): May 24, 2013

Study Record Updates

• Last Update Posted (Actual): November 28, 2017
• Last Update Submitted That Met QC Criteria: November 27, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Breast Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Docetaxel; Paclitaxel
• Other Study ID Numbers: GO27802; 2013-003543-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No