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

Genentech

Status and phase: Completed; Phase 1

Conditions: Breast Cancer, Non-small Lung Cancer

Treatments: Drug: GDC-0032; Drug: Paclitaxel; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01862081

2013-003543-28 (EudraCT Number)

GO27802

Details and patient eligibility

About

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.

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 7 patient groups

Arm A: GDC-0032 + Docetaxel

Experimental group

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.

Treatment:

Drug: GDC-0032

Drug: Docetaxel

Arm B: GDC-0032 + Paclitaxel

Experimental group

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.

Treatment:

Drug: GDC-0032

Drug: Paclitaxel

Arm C: GDC-0032 + Docetaxel

Experimental group

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.

Treatment:

Drug: GDC-0032

Drug: Docetaxel

Arm D: GDC-0032 + Docetaxel

Experimental group

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.

Treatment:

Drug: GDC-0032

Drug: Docetaxel

Arm E: GDC-0032 + Docetaxel

Experimental group

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.

Treatment:

Drug: GDC-0032

Drug: Docetaxel

Arm F: GDC-0032 + Paclitaxel

Experimental group

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.

Treatment:

Drug: GDC-0032

Drug: Paclitaxel

Arm G: GDC-0032 + Paclitaxel

Experimental group

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.

Treatment:

Drug: GDC-0032

Drug: Paclitaxel