Clinical trial NCT02316509: A Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer
Official title: An Open-Label, Phase I Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Seragon Pharmaceuticals
First posted: 2014-12-15
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, dose-finding, safety, pharmacokinetics (PK), and evidence-of-activity study of GDC-0927 in postmenopausal women with locally advanced or metastatic Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 (HER2) breast cancer. The study will be conducted in two parts: Dose escalation and Dose expansion. During dose escalation, GDC-0927 will be administered orally as a single dose on Day -7 for PK evaluation during the lead-in period. Depending on safety and tolerability, participants will be assigned sequentially to escalating doses of GDC-0927 using standard 3+3 design. During dose expansion, there will be no PK week lead-in period. All participants will be treated until disease progression, unacceptable toxicity, participant withdrawal of consent or study termination.


Eligibility 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 tumor, HER2-negative breast cancer
* No prior treatment with GDC-0810 (allowed only during dose expansion stage)
* No more than 2 prior chemotherapies in the advanced or metastatic setting
* 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 endocrine therapy
* At least 3 weeks must have elapsed from the use of any chemotherapy
* Females, 18 years of age or older
* Postmenopausal status as defined by the protocol
* Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to (\</=) 2 (for dose-escalation part) and 0 or 1 (for dose-expansion part)
* Adequate organ function

Exclusion Criteria:

* Untreated or symptomatic brain metastases
* Current treatment with any systemic anti-cancer therapies for advanced disease or any systemic experimental treatment on another clinical trial
* Any of the following within 12 months prior to enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of Grade greater than or equal to (\>/=) 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, or cerebrovascular accident including transient ischemic attack
* Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection
* Known Human Immunodeficiency Virus (HIV) infection
* Major surgery within 4 weeks prior to enrollment
* Radiation therapy within 2 weeks prior to enrollment

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of GDC-0927
timeFrame: Day-7 through Cycle 1 (cycle length: 28 days)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From screening up to approximately 3 years
Secondary outcomes:
measure: Percentage of Participants With Objective Response Assessed by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: At screening, every 8 weeks from Cycle 1 (each cycle: 28 days) up to end of treatment (up to approximately 3 years)
measure: Percentage of Participants With Clinical Benefit Assessed by RECIST v1.1
timeFrame: At screening, every 8 weeks from Cycle 1 (each cycle: 28 days) up to end of treatment (up to approximately 3 years)
measure: Part I: Maximum Observed Plasma Concentration (Cmax) of GDC-0927
timeFrame: Pre-dose (0 hour [hr]), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (cycle length: 28 days)
measure: Part II: Cmax of GDC-0927
timeFrame: Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (each cycle: 28 days)
measure: Part I: Time to Reach Cmax (Tmax) of GDC-0927
timeFrame: Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (cycle length: 28 days)
measure: Part II: Tmax of GDC-0927
timeFrame: Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (each cycle: 28 days)
measure: Part I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0927
timeFrame: Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (cycle length: 28 days)
measure: Part II: AUC of GDC-0927
timeFrame: Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1; pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose on Day 1 Cycle 2 (each cycle: 28 days)
measure: Plasma Half-Life (t1/2) of GDC-0927
timeFrame: Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day -7; Days -5, -4, -3; pre-dose (0 hr) on Day 1 Cycle 1 (cycle length: 28 days)
measure: Part II: t1/2 of GDC-0927
timeFrame: Pre-dose (0 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 hrs post-dose on Day 1 Cycle 1 (each cycle: 28 days)
measure: Part I: Change From Baseline in Corrected QT (QTc) Interval Using Fridericia's Formula, as Assessed by Electrocardiogram (ECG)
timeFrame: Screening (baseline); Days -7, -5, -4, -3; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)
measure: Part II: Change From Baseline in QTc Interval Using Fridericia's Formula, as Assessed by ECG
timeFrame: Screening (baseline); Cycle 1 Day 1; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)
measure: Part I: Change From Baseline in RR Interval, as Assessed by ECG
timeFrame: Screening (baseline); Days -7, -5, -4, -3; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)
measure: Part II: Change From Baseline in RR Interval, as Assessed by ECG
timeFrame: Screening (baseline); Cycle 1 Day 1; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Germantown
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Ctr
state: Tennessee
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO
state: Barcelona
city: San Sebastian
country: Spain
facility: Onkologikoa - Kutxaren Institutu Onkologikoa
state: Guipuzcoa
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid - España; Servicio de Farmacia
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: HM Sanchinarro - CIOCC
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: