GDC-0084 in Combination With Trastuzumab for Patients With HER2-Positive Breast Cancer Brain Metastases

NCT03765983 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 18-516
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a drug called GDC-0084 as a possible treatment for HER2-Positive Breast Cancer. The drugs involved in this study are:

• GDC-0084
• Trastuzumab (Herceptin®)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate in the CNS

  ORR in the CNS according to response assessment in neuro-oncology-brain metastases (RANO-BM) criteria

  2 years

• To evaluate the correlation between inhibition of p-4EBP1 in resected brain tumor tissue and intracranial response in the corresponding patient-derived xenograft (PDX) models of BCBM

  to correlate on-treatment p4EBP1 levels in the resected brain tumor tissue collected from patients to intracranial response to GDC-0084/trastuzumab and survival in the PDX model generated from the same patient

  2 Years

Secondary Outcomes (6)

• CBR

  18 and 24 weeks

• DOR

  2 years

• Objective extra-CNS response rates

  2 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  2 years

• Progression Free Survival

  2 years

Study Arms (2)

Cohort A: single-arm, two stage, phase II cohort

EXPERIMENTAL

GDC-0084 45 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter

Drug: Trastuzumab; Drug: GDC-0084

Cohort B: a pre-surgical window cohort

EXPERIMENTAL

GDC-0084 45 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter Surgical brain metastasis resection

Drug: Trastuzumab; Drug: GDC-0084

Interventions

Trastuzumab DRUG

Trastuzumab is called a "targeted therapy" because it works by attaching itself to specific receptors on the surface of breast cancer cells, known as HER2 receptors. When targeted therapies attach to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the immune system

Cohort A: single-arm, two stage, phase II cohort; Cohort B: a pre-surgical window cohort

GDC-0084 DRUG

GDC-0084 has been shown to stop the activity of a protein called PI3-kinase. This action blocks a pathway in the body that cancer cells commonly use to grow and divide

Cohort A: single-arm, two stage, phase II cohort; Cohort B: a pre-surgical window cohort

Eligibility Criteria

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

You may qualify if:

• Cohort A:
• At least one measurable CNS metastasis, defined as ≥ 10 mm in at least one dimension.
• Unequivocal evidence of new and/or progressive brain metastases, and at least one of the following scenarios:
• Treated with SRS or surgery with residual un-treated lesions remaining. Such participants are eligible for immediate enrollment on this study providing that at least one untreated lesion is measurable
• Participants who have had prior WBRT and/or SRS and then whose lesions have subsequently progressed or who have new lesions are also eligible. In this case, lesions which have been treated with SRS may be considered as target lesions if there is unequivocal evidence, in the opinion of the treating physician, of progression following SRS.
• Participants who have not previously been treated with cranial radiation (e.g., WBRT or SRS) are eligible to enter the study, but such participants must be asymptomatic from their CNS metastases and not requiring corticosteroids for symptom control.
• Participants who present with systemic stable/absent or progressive disease are eligible to this trial, as long as they fulfill one of the above criteria.
• Cohort B:
• New and/or progressive brain metastasis(es) with clinical indication for resection.
• All Cohorts:
• Pathologically confirmed HER2-positive MBC by local laboratory with the following requirements: HER2 overexpressed or amplified (immunohistochemistry of 3+ or HER2 gene amplification by in situ hybridization with a ratio of HER2-gene signals to centromere 17 signals ≥ 2.0 or average HER2 copy number ≥ 6.0 signals/cells).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
• Stable or decreasing corticosteroid dose for at least 7 days prior to initiation of treatment.
• Concurrent administration of other anti-cancer therapy during the course of this study is not allowed. Note that concurrent use of supportive care medications (e.g. anti-resorptive agents, pain medications) is allowed.

You may not qualify if:

• Visceral crisis or impending visceral crisis at time of screening.
• CNS complications for whom urgent neurosurgical intervention is indicated (e.g., resection, shunt placement).
• Known leptomeningeal metastases \[Defined as positive CSF cytology and/or unequivocal radiological evidence of clinically significant leptomeningeal involvement. CSF sampling is not required in the absence of suggestive symptoms to exclude leptomeningeal involvement\].
• Patients with known contraindication to MRI (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity, hypersensitivity, etc.). However, head CT with contrast may be used in place of MRI at baseline and throughout the trial if MRI is contraindicated and a participant's brain metastases are clearly measurable by head CT.
• Chemotherapy or targeted therapy within 14 days prior to initiation of protocol therapy. No washout is required for trastuzumab.
• Has received prior therapy with a PI3K or mTOR inhibitor.
• No washout is required for endocrine therapy. If a patient has been on ovarian suppression for at least 28 days prior to initiation of study treatment, continuation of ovarian suppression is permitted on protocol. Starting a new endocrine therapy during protocol therapy is not permitted.
• Current use or history of receiving a non-approved, investigational treatment within 14 days prior to initiation of protocol therapy.
• Subjects with a history of hypersensitivity to compounds of similar biologic composition to GDC-0084 or any constituent of the product.
• The subject has an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus (DM), gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, or severe malnutrition. If a participant has controlled DM but is unable to monitor blood sugars at home, they will be excluded from the trial.
• The subject is pregnant or breast-feeding.
• No active, second potentially life-threatening cancer.
• Has had major surgery within 21 days before initiation of protocol therapy.
• Active infection requiring IV antibiotics at the time of protocol therapy initiation.
• Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Kazia Therapeutics Limited: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; GDC-0084

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jose P Leone, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 5, 2018
• Study Start: February 11, 2019
• Primary Completion: April 29, 2024
• Study Completion: May 14, 2024
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than one year following the date of publication.
• Access Criteria: Requests may be directed to: \[contact information for Sponsor-Investigator or designee\].

Locations

US (1)