A Study of ARN-810 (GDC-0810) in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01823835
First received: March 25, 2013
Last updated: August 17, 2015
Last verified: August 2015
  Purpose

This study is a multi-institution, Phase I/IIa open-label, dose-finding, safety, pharmacokinetics (PK), and proof-of-concept study of GDC-0810 administered orally on a continuous daily dosing regimen with a PK lead-in period (dose escalation period only). The incidence of dose limiting toxicity will be evaluated from Day -7 through the first cycle of treatment (35 days total). Depending on safety and tolerability, patients will be assigned sequentially to escalating doses of study drug using standard 3+3 design. During the phase IIa portion of the study, there will be no PK lead-in period and all eligible patients will start continuous daily dosing treatment on Cycle 1 Day 1. All patients will be treated until disease progression, unacceptable toxicity, or patient withdrawal of consent.


Condition Intervention Phase
Breast Cancer
Drug: GDC-0810
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Efficacy (phase II portion only):clinical benefit rate according to RECIST v1.1 [ Time Frame: Until disease progression, unacceptable toxicity, or patient withdrawal of consent, approximately 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics of GDC-0810 and its main metabolite: Maximum concentration (Cmax) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of GDC-0810 and its main metabolite: Time to maximum concentration (Tmax) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of GDC-0810 and its main metabolite: area under the concentration-time curve (AUC) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of GDC-0810 and its main metabolite: half-life (t1/2) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 141
Study Start Date: December 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GDC-0810
During dose escalation (phase I), standard 3+3 design will be followed. During dose expansion (phase IIa), new patient cohorts will be enrolled at the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) to further charcterize the safety and pharmacokinetics of the study drug.
Drug: GDC-0810
Oral administration, continuous daily dosing regimen per protocol dose escalation and expansion stages
Other Name: ARN-810

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 ER+ breast cancer
  • ER-positive, 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
  • Females, 18 years of age or older
  • Postmenopausal status
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 2
  • Adequate organ function

Phase II portion

  • All above inclusion criteria, 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 ESR1 mutation and presence of measurable disease as per Response Evaluation Criteria in Solid Tumors (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:

  • Untreated or symptomatic CNS metastases
  • Endometrial disorders
  • More than 1 prior chemotherapy in the advanced/metastatic setting (prior adjuvant chemotherapy is allowed so long as it occurred >/= 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 II portion - all above exclusion criteria, plus:

  • Cohort A1, A2, and Cohort B2 only: > 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. Only) global.rochegenentechtrials@roche.com

Locations
United States, California
Recruiting
San Diego, California, United States, 92103-8465
United States, Connecticut
Not yet 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, 10029
Recruiting
New York, New York, United States, 10065
United States, North Carolina
Not yet recruiting
Charlotte, North Carolina, United States, 28208
United States, Ohio
Not yet 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
Not yet recruiting
Gyeonggi-do, Korea, Republic of, 410-769
Not yet recruiting
Seoul, Korea, Republic of, 152-703
Not yet recruiting
Seoul, Korea, Republic of, 110-774
Not yet recruiting
Seoul, Korea, Republic of, 120-752
Not yet recruiting
Seoul, Korea, Republic of, 138-736
Netherlands
Not yet 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

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01823835     History of Changes
Other Study ID Numbers: GO29642
Study First Received: March 25, 2013
Last Updated: August 17, 2015
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on August 27, 2015