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Breast CancerPhase 2NCT03765983

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

A Phase 2 study testing Trastuzumab and GDC-0084 in people with Breast Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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®) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Trastuzumab and GDC-0084
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
25 Feb 2019to 14 May 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • The participant is ≥18 years old.
  • Participants must have normal organ and marrow function as defined below:
  • Absolute neutrophil count ≥1,000/μl
  • Platelets ≥75,000/μl
  • Hemoglobin ≥9 g/dL
  • Total bilirubin ≤1.5mg/dL (upper limit of normal) except subject with documented Gilbert's syndrome (≤5 x ULN) or liver metastasis, who must have a baseline total bilirubin ≤3.0 mg/dL;
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN OR ≤ 5.0 × institutional ULN for patients with documented liver metastases.
  • Serum creatinine ≤ 1.5 mg/dL (or glomerular filtration rate ≥ 30 ml/min as determined by the Cockcroft-Gault equation)
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 8 days of initiating protocol therapy.
  • The effects of GDC-0084 on the developing human fetus are unknown and radiotherapy has known teratogenic effects so women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 7 months after completion of Trastuzumab administration per recommendations from the Trastuzumab package insert.
  • The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
  • Participant must be able to swallow and retain oral medication.

Who cannot join

  • 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.
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  • 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.
  • Known intolerance to trastuzumab.
  • QT interval time of ≥ 470 msec.
  • Participants receiving any medications or substances that are strong inhibitors or strong inducers of CYP3A4 are ineligible. Should a participant be taking one of these agents and is able to discontinue the therapy or switch to a different agent, no washout will be required prior to starting study medication. Please see Appendix M for the list of medications. Corticosteroids, which are weak CYP3A4 inducers are allowed. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase II Trial of GDC-0084 in Combination With Trastuzumab for Patients With HER2-Positive Breast Cancer Brain Metastases

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®)
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved GDC-0084 as a treatment for any disease.

Trastuzumab is a targeted therapy approved by the FDA to be used alone or in combination with a chemotherapy drug to treat HER2-positive metastatic breast cancer.

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.

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. This process allows trastuzumab to help slow or stop the growth of the breast cancer.

In this research study, the investigators are looking to see how your cancer responds to the combination of GDC-0084 and Trastuzumab.

Conditions
Breast Cancer
Being tested
Trastuzumab, GDC-0084
Keywords
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrastuzumabDrug

    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

  • GDC-0084Drug

    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

Study groups in NCT03765983
Study groupRoleWhat they receive
Cohort A: single-arm, two stage, phase II cohortExperimentalGDC-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
Receives: Drug: Trastuzumab; Drug: GDC-0084
Cohort B: a pre-surgical window cohortExperimentalGDC-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
Receives: Drug: Trastuzumab; Drug: GDC-0084

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate in the CNS

    Defined as the proportion of patients with partial or complete response in the CNS, per RANO-BM criteria (Complete response [CR]: disappearance of all CNS target lesions sustained for at least 4 weeks, no new lesions, no corticosteroids, stable or improved clinically; Partial response [PR]: At least 30% decrease in the sum of longest diameter of CNS target lesions, taking as reference the baseline sum, sustained for at least 4 weeks, no new lesions, stable to decreased corticosteroid dose, stable or improved clinically; Progressive disease [PD]: At least a 20% increase in the sum of longest diameter of CNS target lesions, taking as reference the smallest sum on study; Stable disease [SD]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of long diameter of CNS target lesions while on study; Objective response = CR+PR)

    Measured: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

  2. 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

    Measured: 2 Years

Secondary outcomes (6)

  1. Clinical Benefit Rate in the CNS

    Defined as the proportion of participants with CNS response or stable disease in the CNS >=18 or 24 weeks, per RANO-BM criteria (Complete response [CR]: disappearance of all CNS target lesions sustained for at least 4 weeks, no new lesions, no corticosteroids, stable or improved clinically; Partial response [PR]: At least 30% decrease in the sum of longest diameter of CNS target lesions, taking as reference the baseline sum, sustained for at least 4 weeks, no new lesions, stable to decreased corticosteroid dose, stable or improved clinically; Progressive disease [PD]: At least a 20% increase in the sum of longest diameter of CNS target lesions, taking as reference the smallest sum on study; Stable disease [SD]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of long diameter of CNS target lesions while on study; Clinical benefit 18 weeks = CR+PR+SD>=18 weeks; Clinical benefit 24 weeks = CR+PR+SD>=24 weeks)

    Measured: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks

  2. Clinical Benefit Rate in Extra-CNS

    Defined as the proportion of participants with non-CNS response or stable disease in non-CNS lesions >=18 or 24 weeks, per RECIST 1.1 criteria (Complete response [CR]: Disappearance of all target lesions; Partial response [PR]: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum; Progressive disease [PD]: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study; Stable disease [SD]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters on study; Clinical benefit 18 weeks = CR+PR+SD>=18 weeks; Clinical benefit 24 weeks = CR+PR+SD>=24 weeks)

    Measured: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks

  3. Objective Response Rate in Extra-CNS

    Defined as the proportion of patients with partial or complete response in non-CNS lesions, per RECIST 1.1 criteria (Complete response [CR]: Disappearance of all target lesions; Partial response [PR]: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum; Progressive disease [PD]: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study; Stable disease [SD]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters on study; Objective response = CR+PR)

    Measured: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

  4. Duration of CNS Response

    Defined as the time measurement criteria are met for CR or PR in the CNS (whichever is first recorded) until the first date that progressive disease is objectively documented

    Measured: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

  5. Bi-compartmental Progression-free Survival

    Defined as the time from registration to the first occurrence of progression in the CNS (per RANO-BM criteria), the body (per RECIST 1.1 criteria), or death, whichever comes first. Patients free from progression in the CNS or body are censored at the date of last disease evaluation

    Measured: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

  6. Overall Survival

    Defined as the time from registration to death from any cause. Patients still living are censored at the date last known alive

    Measured: Assessed every 6 months until death of off-study, up to ~62 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2018
  2. Study start25 Feb 2019
  3. Primary completion29 Apr 2024
  4. Study completion14 May 2024

Why it stopped: participants are no longer being examined or receiving intervention

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03765983
Sponsor's protocol ID
18-516
Status last verified
Mar 2026
First submitted
3 Dec 2018
Last updated
27 May 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor-Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab and GDC-0084 in people with Breast Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate in the CNS (time frame: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03765983.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.

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