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

NCT02316509 | Completed Phase 1

• 2 other identifiers: GO296562015-000272-95
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 13

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of GDC-0927

  Day-7 through Cycle 1 (cycle length: 28 days)

• Percentage of Participants With Adverse Events (AEs)

  From screening up to approximately 3 years

Secondary Outcomes (14)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (2)

Part I: Dose Escalation - GDC-0927

EXPERIMENTAL

Participants will receive GDC-0927 orally as a single dose on Day -7. Continuous daily dosing will commence on Day 1. Depending on safety and tolerability, participants will be assigned sequentially to escalating doses of GDC-0927 with use of a standard 3 + 3 design. The starting dose will be 600 milligrams per day (mg/day), followed by dose escalation in 400 milligrams (mg) increments.

Drug: GDC-0927

Part II: Dose Expansion - GDC-0927

EXPERIMENTAL

Participants in the expansion cohorts will receive GDC-0927 at MTD/RP2D starting from Day 1 of Cycle 1 (cycle length: 28 days) up to disease progression, unacceptable toxicity, participant withdrawal of consent or study termination.

Drug: GDC-0927

Interventions

GDC-0927 DRUG

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

Also known as: RO7056119

Part I: Dose Escalation - GDC-0927; Part II: Dose Expansion - GDC-0927

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead
• Seragon Pharmaceuticals: collaborator

Study Sites (13)

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Cancer Center

Germantown, Tennessee, 38138, United States

Location

Vanderbilt Ingram Cancer Ctr

Nashville, Tennessee, 37232, United States

Location

ICO I Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet ICO

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Onkologikoa - Kutxaren Institutu Onkologikoa

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

MD Anderson Cancer Center Madrid - España; Servicio de Farmacia

Madrid, 28033, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28040, Spain

Location

HM Sanchinarro - CIOCC

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 15, 2014
• Study Start: March 17, 2015
• Primary Completion: January 10, 2020
• Study Completion: January 10, 2020
• Last Updated: October 5, 2020

Record last verified: 2020-10

Locations

US (5); ES (8)