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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01862081
• Collaborator: (none)
• Enrollment: 80
• Locations: 14
• Arms: 7
• Actual Duration (Months): 46.8
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer, Non-small Lung Cancer	Drug: Docetaxel; Drug: GDC-0032; Drug: Paclitaxel	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: Jul 16, 2013
• Actual Primary Completion Date: Jun 9, 2017
• Actual Study Completion Date: Jun 9, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Safety: Incidence of adverse events [Approximately 3 years]

2. Safety: Incidence of dose limiting toxicities [Up to 28 days]

Secondary Outcome Measures

1. Area under the curve from time 0 to the last measurable concentration (AUC0-last) [Up to 28 days]

2. Time to maximum observed plasma concentration (Tmax) [Up to 28 days]

3. Maximum observed plasma concentration (Cmax) [Up to 28 days]

4. Minimum observed plasma concentration (Cmin) [Up to 28 days]

5. Objective response according to RECIST v1.1 [Approximately 3 years]

6. Duration of response according to RECIST v1.1 [Approximately 3 years]

7. Progression-free survival (PFS) according to RECIST v1.1 [Approximately 3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT01862081
• Other Study ID Numbers: GO27802; 2013-003543-28
• First Posted: May 24, 2013
• Last Update Posted: Nov 28, 2017
• Last Verified: Nov 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Lung Neoplasms; Paclitaxel; Docetaxel

Study Results

No Results Posted as of Nov 28, 2017