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

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2014-004852-77-ES
• Date of registration: 16/02/2015
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc
• Public title: A Study of ARN-810 (GDC-0810) in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer
• Scientific title: AN OPEN-LABEL, PHASE I/IIA STUDY OF GDC-0810 IN POSTMENOPAUSAL WOMEN WITH LOCALLY ADVANCED OR METASTATIC ESTROGEN RECEPTOR POSITIVE BREAST CANCER
• Date of first enrolment: 27/05/2015
• Target sample size: 141
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004852-77
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Korea, Republic of, Netherlands, Spain, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

Key inclusion & exclusion 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
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 131
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
- Untreated or symptomatic CNS metastases

- Endometrial disorders

- More than 2 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 or any systemic experimental treatment on another clinical trial

- 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 infection

- 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Patients with locally advanced or metastatic estrogen receptor (ER) positive breast cancer
MedDRA version: 17.1 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 100000004864

Intervention(s)

Product Name: GDC-0810
Product Code: RO705-6118/F01-01
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: GDC-0810 (RO7056118)
Other descriptive name: ARN-810
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): 1. Maximum tolerated dose (MTD)
2. Incidence of adverse events
3. Efficacy (phase II portion only):clinical benefit rate according to RECIST v1.1

Secondary Objective: ?To evaluate the safety of GDC-0810 when administered at the RP2D in postmenopausal women with locally advanced or metastatic ER+ (HER2-) breast cancer

?To evaluate the pharmacokinetics of GDC-0810 and its O-glucuronide metabolite following single and multiple dose treatments

?To evaluate the effect of GDC-0810 on ventricular repolarization in postmenopausal women participating in the Phase IIa portion of the study

?To perform exploratory evaluation of biomarkers of pharmacodynamic (PD) response with [18F]-fluoroestradiol (FES) positron emitting tomography (PET) [FES-PET]

?To perform exploratory evaluation of ER target genes expression

?To perform exploratory evaluation of mechanisms of resistance to GDC-0810.

Main Objective: Phase I: To determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) and assess the safety of GDC-0810 in postmenopausal women with locally advanced or metastatic ER+ (HER2-) breast cancer

Phase II: To determine the anti-tumor effect (clinical benefit rate) of GDC-0810 in postmenopausal women with locally advanced or metastatic ER+ (HER2-) breast cancer

Timepoint(s) of evaluation of this end point: 1-2. 12 months
3. Until disease progression, unacceptable toxicity, or patient withdrawal of consent, approximately 6 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-4. 12 months

Secondary end point(s): 1.Pharmacokinetics of ARN-810 and its main metabolite:Maximum concentration (Cmax)
2.Pharmacokinetics of ARN-810 and its main metabolite:Time to maximum concentration (Tmax)
3.Pharmacokinetics of ARN-810 and its main metabolite:area under the concentration-time curve (AUC)
4.Pharmacokinetics of ARN-810 and its main metabolite:half-life (t1/2)

Secondary ID(s)

GO29642

Source(s) of Monetary Support

Genentech Inc. c/o F. Hoffmann-La Roche Ltd