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 September 2015 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01823835
First received: March 25, 2013
Last updated: September 1, 2015
Last verified: September 2015

March 25, 2013
September 1, 2015
December 2014
July 2017   (final data collection date for primary outcome measure)
  • 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 ]
  • Maximum Tolerated Dose (MTD) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of ARN-810 in postmenopausal women with locally advanced or metastatic ER+ (HER2-) breast cancer
  • To determine the safety of ARN-810 and its O-glucuronide metabolite in postmenopausal women with locally advanced or metastatic ER+ (HER2-) breast cancer [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Incidence of treatment-emergent adverse events will be summarized by severity and relationship to study drug. Clinical laboratory results, vital signs, use of concomitant medications and treatments, and endometrial thickness will be summarized with descriptive statistics (such as mean, median, standard deviation and range for continuous data, and percentages for categorical data).
Complete list of historical versions of study NCT01823835 on ClinicalTrials.gov Archive Site
  • 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 ]
Pharmacokinetics (PK) of ARN-810 and its O-glucuronide metabolite [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Full plasma PK profiles (Cmax, Tmax, AUC, T1/2) will be obtained for ARN-810 and its O-glucuronide metabolite and analyzed using non-compartmental methods.
Not Provided
Not Provided
 
A Study of ARN-810 (GDC-0810) in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer
Not Provided

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
Drug: GDC-0810
Oral administration, continuous daily dosing regimen per protocol dose escalation and expansion stages
Other Name: ARN-810
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.
Intervention: Drug: GDC-0810
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
141
July 2017
July 2017   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact: Reference Study ID Number: GO29642 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com
United States,   Korea, Republic of,   Netherlands,   Spain
 
NCT01823835
GO29642
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Genentech, Inc.
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP