A Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or a Luteinizing Hormone-releasing Hormone (LHRH) Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01823835
First received: March 25, 2013
Last updated: April 28, 2016
Last verified: April 2016
  Purpose
This study is a multi-institution, Phase Ia/Ib/IIa open-label, dose-finding, safety, pharmacokinetics (PK), and proof-of-concept study of GDC-0810 as a single agent and in combination with palbociclib and/or LHRH agonist. The study is divided into 3 phases: Phase Ia, Phase Ib, and Phase IIa. During Phase Ia (dose escalation phase), GDC-0810 single agent will be administered orally on a continuous daily dosing regimen with a Day -7 lead-in period for single dose PK evaluation prior to the start of daily treatment. The incidence of dose-limiting toxicities (DLTs) will be evaluated from Day -7 through the first cycle (28 days) of treatment (35 days total). Depending on safety and tolerability, participants will be assigned sequentially to escalating doses of GDC-0810 using standard 3 + 3 design. During Phase Ib (dose escalation and expansion phase), participants will receive GDC-0810 with palbociclib and/or LHRH agonist to determine the recommended Phase II dose (RP2D) and assess the safety and tolerability of concomitant administration. During Phase IIa (dose expansion phase), participants previously treated with an aromatase inhibitor (AI) will be treated at the RP2D to further characterize the safety, PK, pharmacodynamics, and anti-tumor activity of GDC-0810.

Condition Intervention Phase
Breast Cancer
Drug: GDC-0810
Drug: LHRH Agonist
Drug: Palbociclib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Phase Ib: RP2D of GDC-0810 When Used in Combination With Palbociclib and/or LHRH [ Time Frame: first cycle (Days 1 to 28 of a 28-day schedule) ] [ Designated as safety issue: Yes ]
  • Phase IIa: Percentage of Participants With Confirmed Objective Tumor Response of GDC-0810 According to RECIST v1.1 [ Time Frame: Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years) ] [ Designated as safety issue: No ]
  • Phase Ia: Maximum Tolerated Dose (MTD) of GDC-0810 When Used as a Single Agent [ Time Frame: Day -7 through the first cycle (28 days) of treatment (35 days total) ] [ Designated as safety issue: Yes ]
  • Phase Ia: RP2D of GDC-0810 When Used as a Single Agent [ Time Frame: Day -7 through the first cycle (28 days) of treatment (35 days total) ] [ Designated as safety issue: Yes ]
  • Phase IIa: Percentage of Participants With Clinical Benefit Response of GDC-0810 According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Screening and every 8 weeks from Cycle 1 Day 1 until Cycle 12, thereafter every 3 months until disease progression (up to 3 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase IIa: Effect of GDC-0810 Single Agent on Ventricular Repolarization as Measured by Corrected QT Intervals (QTc) Using Fridericia's Formula [ Time Frame: Screening; on Cycle 2 Day 1 predose and at 1, 2, 3, 4, and 6 hours postdose; Cycle 3 Day 1 predose, and at 1, 3, and 6 hours post dose ] [ Designated as safety issue: No ]
  • Phase Ib: Cmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist [ Time Frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1, C2, C3, D1,and D2), Cycle 1 Day 8 (Cohorts C1, C2, and C3), and Cycle 2 Day 1 (Cohorts D1 and D2) ] [ Designated as safety issue: No ]
  • Phase Ib: Tmax of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist [ Time Frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1, C2, C3, D1,and D2), Cycle 1 Day 8 (Cohorts C1, C2, and C3), and Cycle 2 Day 1 (Cohorts D1 and D2) ] [ Designated as safety issue: No ]
  • Phase Ib: AUC of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist [ Time Frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1, C2, C3, D1,and D2), Cycle 1 Day 8 (Cohorts C1, C2, and C3), and Cycle 2 Day 1 (Cohorts D1 and D2) ] [ Designated as safety issue: No ]
  • Phase Ib: t/2 of GDC-0810 in Combination With Palbociclib and/or an LHRH Agonist [ Time Frame: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (Cohorts C1, C2, C3, D1,and D2), Cycle 1 Day 8 (Cohorts C1, C2, and C3), and Cycle 2 Day 1 (Cohorts D1 and D2) ] [ Designated as safety issue: No ]
  • Phase Ib: Cmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist [ Time Frame: Cohorts C1, C2, C3: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8 ] [ Designated as safety issue: No ]
  • Phase Ib: Tmax of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist [ Time Frame: Cohorts C1, C2, C3: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8 ] [ Designated as safety issue: No ]
  • Phase Ib: AUC of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist [ Time Frame: Cohorts C1, C2, C3: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8 ] [ Designated as safety issue: No ]
  • Phase Ib: t/2 of Palbociclib in Combination With GDC-0810 and/or an LHRH Agonist [ Time Frame: Cohorts C1, C2, C3: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 8 ] [ Designated as safety issue: No ]
  • Phase Ib: Cmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib [ Time Frame: Cohorts D1 and D2: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Phase Ib: Tmax of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib [ Time Frame: Cohorts D1 and D2: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Phase Ib: AUC of LHRH Agonist in Combination With GDC-0810 and/or an Palbociclib [ Time Frame: Cohorts D1 and D2: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Phase Ib: t/2 of LHRH Agonist in Combination With GDC-0810 and/or Palbociclib [ Time Frame: Cohorts D1 and D2: Predose and at 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • All Phases: Number of Participants With Adverse Events [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Phase Ia: Maximum Plasma Concentration (Cmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites [ Time Frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 (Day -6), and 48 (Day -5) hours postdose; Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose (Cycle 2 Day 2, prior to the next dose) ] [ Designated as safety issue: No ]
  • Phase Ia: Time to Maximum Concentration (Tmax) of GDC-0810 Single Agent and Its Glucuronide Metabolites [ Time Frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 (Day -6), and 48 (Day -5) hours postdose; Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose (Cycle 2 Day 2, prior to the next dose) ] [ Designated as safety issue: No ]
  • Phase Ia: Area Under the Concentration-time Curve (AUC) of GDC-0810 Single Agent and Its Glucuronide Metabolites [ Time Frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 (Day -6), and 48 (Day -5) hours postdose; Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose (Cycle 2 Day 2, prior to the next dose) ] [ Designated as safety issue: No ]
  • Phase Ia: Plasma Half-life (t1/2) of GDC-0810 Single Agent and Its Glucuronide Metabolites [ Time Frame: Day -7 at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 (Day -6), and 48 (Day -5) hours postdose; Day 29 (Cycle 2 Day 1) at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose (Cycle 2 Day 2, prior to the next dose) ] [ Designated as safety issue: No ]

Estimated Enrollment: 195
Study Start Date: December 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GDC-0810 + Palbociclib and/or an LHRH Agonist
The starting dose for Cohort C1 dose escalation of GDC-0810 will be 400 mg per day on Days 1 to 28 of a 28-day schedule, taken together with 125 mg palbociclib administered on Days 1 to 21 of a 28-day schedule. Dose escalation will be performed in Cohorts C1 and C2. In Cohort C3, participants will receive the RP2D of GDC-0810 in combination with palbociclib identified in during dose escalation and participants may also receive LHRH every 4 weeks. In Cohort D1 and Cohort D2, GDC-0810 600 mg will be administered orally on Days 1 to 28 of a 28-day schedule and an LHRH agonist administered monthly. Treatments will continue until disease progression, unacceptable toxicity, or withdrawal of consent (up to 3 years).
Drug: LHRH Agonist
LHRH agonist will be administered once monthly until disease progression, unacceptable toxicity, or withdrawal of consent (up to 3 years). Choice of LHRH agonist will be an institutional choice approved for use in breast cancer.
Drug: Palbociclib
Palbociclib will be administered orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent (up to 3 years).
Experimental: GDC-0810 Single Agent
During dose escalation (Phase I), GDC-0810 will be administered orally once daily in ascending-dose levels with a starting dose of 100 milligrams (mg) once daily. During dose expansion (Phase IIa), GDC-0810 will be administered at the MTD or RP2D define in dose escalation part of the study. Treatments will continue until disease progression, unacceptable toxicity, or withdrawal of consent (up to 3 years).
Drug: GDC-0810
GDC-0810 will be administered orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent (up to 3 years).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Phase 1a portion

  • Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of either locally recurrent disease not amenable to resection or radiation therapy with curative intent, or metastatic disease, both progressing after at least 6 months of hormonal therapy for estrogen receptor (ER) positive breast cancer
  • ER-positive, human epidermal growth factor 2 (HER2) negative
  • At least 2 months must have elapsed from the use of tamoxifen
  • At least 6 months must have elapsed from the use of fulvestrant
  • At least 2 weeks must have elapsed from the use of any other anticancer hormonal therapy
  • At least 3 weeks must have elapsed from the use of any chemotherapy
  • Postmenopausal status
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
  • Adequate organ function

Phase Ib portion

  • All above inclusion criteria, except:
  • Postmenopausal status, pre- and peri-menopausal participants will also be included
  • ECOG performance status less than 2
  • At least 2 months must have elapsed from the use of tamoxifen not applicable
  • At least 6 months must have elapsed from the use of fulvestrant not applicable

and plus:

  • Documented sensitivity to prior hormonal therapy
  • Cohorts C0, C1, C2, and C3 (palbociclib combination cohorts): no prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitor

Phase IIa portion

  • All above inclusion criteria for Phase Ia, except:
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • At least 6 months must have elapsed from the use of fulvestrant not applicable

and plus:

  • Cohort A only: confirmed estrogen receptor alpha (ESR1) mutation and presence of measurable disease as per RECIST v1.1 or evaluable bone disease
  • Cohort A1 only: no prior fulvestrant allowed; at least 2 months must have elapsed from the use of tamoxifen
  • Cohort A2 only: prior fulvestrant allowed
  • Cohort B only: disease progression following no more than 1 prior treatment with an aromatase inhibitor in the advanced/metastatic setting
  • Cohort B1 only: no prior fulvestrant allowed
  • Cohort B2 only: prior fulvestrant allowed

Exclusion Criteria:

Phase 1a portion

  • Untreated or symptomatic central nervous system (CNS) metastases
  • Endometrial disorders
  • More than 2 prior chemotherapy in the advanced/metastatic setting (prior adjuvant chemotherapy is allowed so long as it occurred greater than or equal to 12 months prior to enrollment)
  • Current treatment with any systemic anticancer therapies for advanced disease
  • Any significant cardiac dysfunction within 12 months prior to enrollment
  • Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection
  • Known human immunodeficiency virus (HIV) infection
  • Known clinically significant history of liver disease
  • Major surgery within 4 weeks prior to enrollment
  • Radiation therapy within 2 weeks prior to enrollment

Phase Ib portion - all above exclusion criteria, plus:

  • Cohorts C0, C1, C2 or C3 (palbociclib combination cohorts): history of venous thromboembolic event requiring therapeutic anticoagulation; vaginal bleeding within 2 months prior to enrollment

Phase IIa portion - all above exclusion criteria, plus:

  • Cohort A1, A2, and Cohort B2 only: more than 1 prior chemotherapy in the advanced/metastatic setting
  • Cohort B1 only: prior chemotherapy in the advanced/metastatic setting
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01823835

Contacts
Contact: Reference Study ID Number: GO29642 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
United States, California
Recruiting
San Diego, California, United States, 92103-8465
United States, Connecticut
Recruiting
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02114
Recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
Recruiting
St. Louis, Missouri, United States, 63128
United States, New York
Recruiting
New York, New York, United States, 10065
Recruiting
New York, New York, United States, 10029
United States, North Carolina
Recruiting
Charlotte, North Carolina, United States, 28208
United States, Ohio
Recruiting
Cleveland, Ohio, United States, 44106
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37232
United States, Washington
Recruiting
Seattle, Washington, United States, 98109
Korea, Republic of
Recruiting
Gyeonggi-do, Korea, Republic of, 10408
Recruiting
Seoul, Korea, Republic of, 03722
Recruiting
Seoul, Korea, Republic of, 08308
Recruiting
Seoul, Korea, Republic of, 138-736
Recruiting
Seoul, Korea, Republic of, 03080
Netherlands
Recruiting
Amsterdam, Netherlands, 1081 HV
Recruiting
Groningen, Netherlands, 9700 RB
Spain
Recruiting
Barcelona, Spain, 08035
Recruiting
Madrid, Spain, 28050
Recruiting
Valencia, Spain, 46010
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01823835     History of Changes
Other Study ID Numbers: GO29642  2014-004852-77 
Study First Received: March 25, 2013
Last Updated: April 28, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Palbociclib
Prolactin Release-Inhibiting Factors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2016