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

• ClinicalTrials.gov Identifier: NCT01862081
• Recruitment Status: Completed
• First Posted: May 24, 2013
• Last Update Posted: November 28, 2017
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: May 22, 2013
• First Posted Date: May 24, 2013
• Last Update Posted Date: November 28, 2017
• Actual Study Start Date: July 16, 2013
• Actual Primary Completion Date: June 9, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 22, 2013)

• Safety: Incidence of adverse events [ Time Frame: Approximately 3 years ]
• Safety: Incidence of dose limiting toxicities [ Time Frame: Up to 28 days ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 17, 2015)

• Area under the curve from time 0 to the last measurable concentration (AUC0-last) [ Time Frame: Up to 28 days ]
• Time to maximum observed plasma concentration (Tmax) [ Time Frame: Up to 28 days ]
• Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 28 days ]
• Minimum observed plasma concentration (Cmin) [ Time Frame: Up to 28 days ]
• Objective response according to RECIST v1.1 [ Time Frame: Approximately 3 years ]
• Duration of response according to RECIST v1.1 [ Time Frame: Approximately 3 years ]
• Progression-free survival (PFS) according to RECIST v1.1 [ Time Frame: Approximately 3 years ]

Original Secondary Outcome Measures (submitted: May 22, 2013)

• Area under the curve from time 0 to the last measurable concentration [ Time Frame: Up to 28 days ]
• Time to maximum observed plasma concentration [ Time Frame: Up to 28 days ]
• Maximum observed plasma concentration [ Time Frame: Up to 28 days ]
• Minimum observed plasma concentration [ Time Frame: Up to 28 days ]
• Objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Approximately 3 years ]
• Duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Approximately 3 years ]
• Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Approximately 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Official Title: Not Provided
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer, Non-small Lung Cancer

Intervention

• 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.
• Drug: Paclitaxel
  Participants will receive paclitaxel 80 mg/m^2 IV dose on Day 1, 8, 15 and 22 of each 28-day cycle.

Study Arms

• 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.
  Interventions:

  • Drug: Docetaxel
  • Drug: GDC-0032
• 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.
  Interventions:

  • Drug: GDC-0032
  • Drug: Paclitaxel
• 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.
  Interventions:

  • Drug: Docetaxel
  • Drug: GDC-0032
• 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.
  Interventions:

  • Drug: Docetaxel
  • Drug: GDC-0032
• 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.
  Interventions:

  • Drug: Docetaxel
  • Drug: GDC-0032
• 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.
  Interventions:

  • Drug: GDC-0032
  • Drug: Paclitaxel
• 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.
  Interventions:

  • Drug: GDC-0032
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 24, 2017): 80
• Original Estimated Enrollment (submitted: May 22, 2013): 65
• Actual Study Completion Date: June 9, 2017
• Actual Primary Completion Date: June 9, 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Spain, United States

Administrative Information

• NCT Number: NCT01862081
• Other Study ID Numbers: GO27802; 2013-003543-28 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: November 2017