A Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Breast Cancer Clinical Trial

Official title:

An Open-Label, Phase I Study of GDC-0927 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02316509
• Other study ID #: GO29656
• Secondary ID: 2015-000272-95
• Status: Completed
• Phase: Phase 1
• Start date: March 17, 2015
• Est. completion date: January 10, 2020

Study information

• Verified date: October 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: January 10, 2020
• Est. primary completion date: January 10, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• GDC-0927
GDC-0927 will be administered as per schedule specified in the respective arm.

Locations

Country	Name	City	State
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO	L'Hospitalet de Llobregat	Barcelona
Spain	HM Sanchinarro - CIOCC	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	MD Anderson Cancer Center Madrid - España; Servicio de Farmacia	Madrid
Spain	Onkologikoa - Kutxaren Institutu Onkologikoa	San Sebastian	Guipuzcoa
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	Sarah Cannon Cancer Center	Germantown	Tennessee
United States	Vanderbilt Ingram Cancer Ctr	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	Seragon Pharmaceuticals

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of GDC-0927		Day-7 through Cycle 1 (cycle length: 28 days)
Primary	Percentage of Participants With Adverse Events (AEs)		From screening up to approximately 3 years
Secondary	Percentage of Participants With Objective Response Assessed by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)		At screening, every 8 weeks from Cycle 1 (each cycle: 28 days) up to end of treatment (up to approximately 3 years)
Secondary	Percentage of Participants With Clinical Benefit Assessed by RECIST v1.1		At screening, every 8 weeks from Cycle 1 (each cycle: 28 days) up to end of treatment (up to approximately 3 years)
Secondary	Part I: Maximum Observed Plasma Concentration (Cmax) of GDC-0927		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)
Secondary	Part II: Cmax of GDC-0927		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)
Secondary	Part I: Time to Reach Cmax (Tmax) of GDC-0927		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)
Secondary	Part II: Tmax of GDC-0927		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)
Secondary	Part I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GDC-0927		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)
Secondary	Part II: AUC of GDC-0927		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)
Secondary	Plasma Half-Life (t1/2) of GDC-0927		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)
Secondary	Part II: t1/2 of GDC-0927		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)
Secondary	Part I: Change From Baseline in Corrected QT (QTc) Interval Using Fridericia's Formula, as Assessed by Electrocardiogram (ECG)		Screening (baseline); Days -7, -5, -4, -3; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)
Secondary	Part II: Change From Baseline in QTc Interval Using Fridericia's Formula, as Assessed by ECG		Screening (baseline); Cycle 1 Day 1; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)
Secondary	Part I: Change From Baseline in RR Interval, as Assessed by ECG		Screening (baseline); Days -7, -5, -4, -3; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)
Secondary	Part II: Change From Baseline in RR Interval, as Assessed by ECG		Screening (baseline); Cycle 1 Day 1; Cycle 2 Day 1; end of treatment (up to approximately 3 years) (each cycle = 28 days)