AzTrials
AzTrials

Brain MetastasesPhase 1NCT04192981

GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases

A Phase 1 study testing GDC-0084 and whole brain radiation therapy radiation in people with Brain Metastases and Leptomeningeal Metastasis, run by Memorial Sloan Kettering Cancer Center at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study will test the safety of the study drug, GDC-0084, in combination with radiation therapy in people who have solid tumor brain metastases or leptomeningeal metastases. All participants will have cancer with a PIK3CA mutation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Metastases, Leptomeningeal Metastasis
What is being tested?
GDC-0084 and whole brain radiation therapy radiation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
9 sitesUnited States
Study dates
6 Dec 2019to Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Histologically confirmed solid tumor malignancies harboring PIK3CA mutations which include mutations in any of the following genes: PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3C2G, PIK3C3, INPP4A, INPP4B, INPPL1, INPP5D, PTEN, AKT1, AKT2, AKT3, and MTOR.
  • Brain metastases and/or leptomeningeal metastases involving the brain demonstrated by MR imaging of the brain. For patients with brain metastases, measurable lesion by RANO-BM is required28. Patients with spine leptomeningeal metastases are eligible for the study if they have leptomeningeal metastases of the brain demonstrated by MRI imaging of the brain.
  • KPS ≥ 70
  • Age ≥ 18 years
  • Able to provide informed consent.
  • If a patient is on corticosteroid, he/she must be on a stable daily dose of < 4mg dexamethasone or equivalent. Patient does not need to be given corticosteroid as prophylaxis if not clinically indicated.
Show all 21Show fewer
  • No limit to prior therapies with the last systemic therapy ≥ 1 week from initiation of protocol therapy. Systemic therapy can resume after completion of protocol DLT assessment period.
  • Patients with prior SRS are eligible, provided that there are new, non-irradiated brain lesions or leptomeningeal metastases. Patients must be ≥ 3 months post prior cranial radiation therapy.
  • Patients with seizure history related to brain metastases or leptomeningeal metastases controlled on antiepileptic medications are eligible.
  • Patient at reproductive potential must agree to practice an effective contraceptive method
  • Patient must be able to swallow and retain oral medication
  • Adequate organ function as assessed by laboratory tests.
  • Adequate bone marrow function
  • Hemoglobin ≥ 8g/dL
  • Absolute neutrophil count ≥1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Adequate liver function
  • Bilirubin ≤1.5 times upper limit normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2 times ULN
  • Adequate renal function ° BUN and Creatinine ≤ 1.5 times ULN

Who cannot join

  • Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects tissue tolerances
  • Patients with brain metastases eligible for single fraction stereotactic radiation therapy
  • Serious medical co-morbidities precluding radiotherapy
  • Insulin-treated diabetes; subjects with diabetes or impaired glucose tolerance that is not treated with insulin may be enrolled
  • QT interval ≥ 450 msec on EKG
  • Cardiac dysfunction defined as: myocardial infarction within 6 months of study entry, NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias
Show all 10Show fewer
  • Known hypersensitivity or intolerance to GDC-0084 or to any other inhibitor of the PI3K/ Akt/ mTOR pathway
  • Past medical history of interstitial lung disease, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease
  • Subject receiving any medications or substances that are moderate and/or potent enzyme inducers or inhibitors which may have an effect on the metabolism of GDC-0084.
  • Pregnant or lactating women.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Memorial Sloan Kettering Basking Ridge (Consent only)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack (Consent only)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (All protocol activities)

    Harrison, New York, 10604

  • BAPTIST ALLIANCE - MCI (Data Collection Only)

    Miami, Florida, 33143

  • Memorial Sloan Kettering Monmouth (All protocol activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Consent only)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All protocol activities)

    New York, New York, 10065

  • University of Washington (Data Collection AND Data Analysis)

    Seattle, Washington, 98109

  • Memorial Sloan Kettering Nassau (Consent only)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: A Phase I Study With Expansion Cohort of Concurrent GDC-0084 With Radiation Therapy for Patients With Solid Tumor Brain Metastases or Leptomeningeal Metastases Harboring PI3K Pathway Mutations

This study will test the safety of the study drug, GDC-0084, in combination with radiation therapy in people who have solid tumor brain metastases or leptomeningeal metastases. All participants will have cancer with a PIK3CA mutation. The researchers will test increasing doses of GDC-0084 to find the highest dose that causes few or mild side effects in participants. The study will also try to find out if the combination of the study drug with radiation is effective against participants' cancer.

Being tested
GDC-0084, whole brain radiation therapy radiation
Keywords
GDC-0084, Radiation, PIK3CA Mutations, 19-359
Medical subject headings
Brain Neoplasms, Meningeal Carcinomatosis

What participants receive

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

  • GDC-0084Drug

    GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily

  • whole brain radiation therapy radiationRadiation

    30Gy in 10 fractions

Study groups in NCT04192981
Study groupRoleWhat they receive
Concurrent GDC-0084 with RadiationExperimentalGDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily, with a potential de-escalation cohort to 30mg, to determine MTD in combination with whole brain radiation therapy radiation therapy to 30Gy in 10 fractions. Once MTD is determined, 12 additional patients will be treated with GDC-0084 at MTD in combination with whole brain radiation therapy.
Receives: Drug: GDC-0084; Radiation: whole brain radiation therapy radiation

What is being measured

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

  1. maximum tolerated dose (MTD)

    Four dose levels will be examined and the maximum tolerated dose (MTD) will be identified.

    The standard 3+3 dose-escalation scheme for this study is as follows. Patients will be accrued to the study in cohorts of 3. For any given dose an initial cohort of 3 patients will be treated at that dose.The dose level will be escalated if none of the 3 exhibits any dose limiting toxicity (DLT).

    Measured: 1 year

Secondary outcomes (1)

  1. local recurrence rate

    For patients with brain metastases, response determination will be determined using Response Assessment in Neuro-Oncology Brain Metastases criteria28. For patients with leptomeningeal metastases, response assessment will be determined by investigator based on MRI.

    Measured: 1 year

Timeline

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

  1. First posted10 Dec 2019
  2. Study start6 Dec 2019
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single-arm, prospective trial
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04192981
Sponsor's protocol ID
19-359
Status last verified
Apr 2026
First submitted
6 Dec 2019
Last updated
22 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GDC-0084 and whole brain radiation therapy radiation in people with Brain Metastases and Leptomeningeal Metastasis, run by Memorial Sloan Kettering Cancer Center at 9 sites 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 21 inclusion and 10 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: under way, not looking for participants, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

maximum tolerated dose (MTD) (time frame: 1 year). 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 NCT04192981.

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 22 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in