A Study of Paclitaxel With GDC-0941 Versus Paclitaxel With Placebo in Participants With Locally Recurrent or Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT01740336
• Recruitment Status: Completed
• First Posted: December 4, 2012
• Last Update Posted: April 24, 2017
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: November 30, 2012
• First Posted Date: December 4, 2012
• Last Update Posted Date: April 24, 2017
• Actual Study Start Date: February 6, 2013
• Actual Primary Completion Date: October 20, 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 21, 2017): Progression-Free Survival (PFS) Assessed as per Modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) [ Time Frame: From the time of randomization until disease progression or death from any cause (up to approximately 3 years) ]
• Original Primary Outcome Measures (submitted: November 30, 2012): Progression-free survival (PFS), defined as time from randomization to disease progression (tumor assessments according to RECIST v.1.1 criteria) or death from any cause [ Time Frame: approximately 3.5 years ]

Current Secondary Outcome Measures (submitted: April 21, 2017)

• Percentage of Participants With Adverse Events [ Time Frame: From randomization up to approximately 3 years ]
• Percentage of Participants With Objective Tumor Response Assessed as per Modified RECIST v1.1 [ Time Frame: From first observation of an objective tumor response until disease progression (up to approximately 3 years) ]
• Percentage of Participants Acheiving Clinical Benefit (Partial Response, Complete Response or Stable Disease Lasting for at Least 6 Months) Assessed as per Modified RECIST v1.1 [ Time Frame: From randomization until disease progression (up to approximately 3 years) ]
• Duration of Confirmed Objective Response Assessed as per Modified RECIST v1.1 [ Time Frame: From first observation of an objective tumor response until disease progression (up to approximately 3 years) ]
• Population Pharmacokinetics (PK) for GDC-0941 [ Time Frame: Day 8 of Cycle 1 and Day 1 of Cycle 6 (cycle length=28 days) ]
• Population PK for Paclitaxel [ Time Frame: Day 1 of Cycle 1 (cycle length=28 days) ]

Original Secondary Outcome Measures (submitted: November 30, 2012)

• Safety: Incidence of adverse events [ Time Frame: approximately 3.5 years ]
• Objective tumor response rate [ Time Frame: approximately 3.5 years ]
• Clinical benefit rate, defined as partial response, complete response or stable disease lasting at least 6 months [ Time Frame: approximately 3.5 years ]
• Duration of confirmed objective response [ Time Frame: approximately 3.5 years ]

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

Descriptive Information

• Brief Title: A Study of Paclitaxel With GDC-0941 Versus Paclitaxel With Placebo in Participants With Locally Recurrent or Metastatic Breast Cancer
• Official Title: A Phase II, Randomized Study of Paclitaxel With GDC-0941 Versus Paclitaxel With Placebo in Patients With Locally Recurrent or Metastatic Breast Cancer
• Brief Summary: This multicenter, randomized, single-blind, placebo-controlled, two arm study will evaluate the efficacy and safety of paclitaxel with GDC-0941 versus paclitaxel with placebo in participants with locally recurrent or metastatic breast cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: GDC-0941
  GDC-0941 will be administered QD orally for 5 consecutive days each week.
• Drug: Placebo
  Placebo matching to GDC-0941
• Drug: Paclitaxel
  Paclitaxel will be administered IV weekly for 3 out of 4 weeks in every 28-day cycle.

Study Arms

• Experimental: A: Paclitaxel, GDC-0941
  Participants will receive GDC-091 260 milligrams (mg) orally in repeated rounds of once daily (QD) dosing for 5 consecutive days followed by 2 consecutive days during which GDC-0941 will not be administered (5/7-day schedule). This 5/7-day schedule will be repeated weekly in each 28-day cycle until disease progression or intolerable toxicity. Participants will receive 90 milligrams per square meter (mg/m^2) intravenously (IV) weekly for 3 out of 4 weeks in every 28-day cycle.
  Interventions:

  • Drug: GDC-0941
  • Drug: Paclitaxel
• Placebo Comparator: B: Paclitaxel, Placebo
  Participants will receive placebo matching to GDC-0941 on the 5/7-day schedule along with 90 mg/m^2 IV weekly for 3 out of 4 weeks in every 28-day cycle.
  Interventions:

  • Drug: Placebo
  • Drug: Paclitaxel

• Publications *: Vuylsteke P, Huizing M, Petrakova K, Roylance R, Laing R, Chan S, Abell F, Gendreau S, Rooney I, Apt D, Zhou J, Singel S, Fehrenbacher L. Pictilisib PI3Kinase inhibitor (a phosphatidylinositol 3-kinase [PI3K] inhibitor) plus paclitaxel for the treatment of hormone receptor-positive, HER2-negative, locally recurrent, or metastatic breast cancer: interim analysis of the multicentre, placebo-controlled, phase II randomised PEGGY study. Ann Oncol. 2016 Nov;27(11):2059-2066. doi: 10.1093/annonc/mdw320. Epub 2016 Aug 29.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 21, 2017): 183
• Original Estimated Enrollment (submitted: November 30, 2012): 180
• Actual Study Completion Date: December 10, 2015
• Actual Primary Completion Date: October 20, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease
• Human epidermal growth factor receptor 2 (HER2)-negative and hormone receptor (HR) (estrogen receptor and/or progesterone receptor)-positive disease as defined by local guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematologic and end organ function
• Women of childbearing potential must agree to remain abstinent or to use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1 percent (%) per year, during the treatment period and for at least 30 days after the last dose of study treatment or 6 months after discontinuation of paclitaxel, whichever is longer

Exclusion Criteria:

• Prior non-capecitabine chemotherapy for locally recurrent or metastatic disease
• Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor for advanced or metastatic breast cancer
• History of intolerance to a taxane-containing therapy
• History of clinically significant cardiac or pulmonary dysfunction
• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Clinically significant history of liver disease
• Active autoimmune disease or active inflammatory disease
• Immunocompromised status due to current known active infection with human immunodeficiency virus (HIV) or due to the use of immunosuppressive therapies for other conditions
• Need for current chronic corticosteroid therapy
• Pregnant, lactating, or breastfeeding women
• Current severe, uncontrolled systemic disease
• Known untreated or active central nervous system (CNS) metastases

Sex/Gender

• Sexes Eligible for Study: Female

• 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: Australia, Austria, Belgium, Czechia, Korea, Republic of, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01740336
• Other Study ID Numbers: GO28509; 2012-003262-41 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• 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: April 2017