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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

NCT01862081

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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:

Clinical Trial IDs

  • ORG STUDY ID: GO27802
  • SECONDARY ID: 2013-003543-28
  • NCT ID: NCT01862081

Conditions

  • Breast Cancer, Non-small Lung Cancer

Interventions

DrugSynonymsArms
DocetaxelArm A: GDC-0032 + Docetaxel
GDC-0032Arm A: GDC-0032 + Docetaxel
PaclitaxelArm B: GDC-0032 + Paclitaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A: GDC-0032 + DocetaxelExperimentalParticipants 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.
  • Docetaxel
  • GDC-0032
Arm B: GDC-0032 + PaclitaxelExperimentalParticipants 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.
  • GDC-0032
  • Paclitaxel
Arm C: GDC-0032 + DocetaxelExperimentalParticipants 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.
  • Docetaxel
  • GDC-0032
Arm D: GDC-0032 + DocetaxelExperimentalParticipants 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.
  • Docetaxel
  • GDC-0032
Arm E: GDC-0032 + DocetaxelExperimentalParticipants 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.
  • Docetaxel
  • GDC-0032
Arm F: GDC-0032 + PaclitaxelExperimentalParticipants 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.
  • GDC-0032
  • Paclitaxel
Arm G: GDC-0032 + PaclitaxelExperimentalParticipants 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.
  • GDC-0032
  • Paclitaxel

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Incidence of adverse events
Time Frame:Approximately 3 years
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Genentech, Inc.

Last Updated

November 27, 2017