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Low-grade GliomaPhase 1NCT03429803

DAY101 In Gliomas and Other Tumors

A Phase 1 study testing DAY101 in people with Low-grade Glioma, run by Karen D. Wright, MD at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This research study is studying a drug Tovorafenib/DAY101 (formerly TAK-580, MLN2480) as a possible treatment a low-grade glioma that has not responded to other treatments. The name of the study drug involved in this study is: Tovorafenib/DAY101 (formerly TAK-580, MLN2480) Read more about this study

Who is it for?
Ages 1 year to 25 years
Conditions the study is for
Low-grade Glioma
What is being tested?
DAY101
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
15 sitesUnited States
Study dates
27 Feb 2018to 31 Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

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 1 year to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Participants must meet the following criteria on screening examination to be eligible to participate in the study:
  • Phase I
  • Pediatric patients with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1.
  • Mutational status requires a pathology report, genomic sequencing, or immunohistochemical report of a mutation or activation of the RAS/RAF/MEK/ERK pathway.
  • The remaining criteria include:
  • Patients must be >1 year and <25 years old.
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  • Patients must have adequate performance status:
  • Karnofsky ≥ 50 for patients ≥ 16 years of age (See Appendix A).
  • Lansky ≥ 50 for patients < 16 years of age (See Appendix A).
  • Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score (See Appendix A).
  • A patient who has failed standard therapy. Note: standard of care for resectable low grade glioma, as an example, is surgery. Therefore, patients with low grade glioma that recurs after presumed gross total resection may enroll without prior chemotherapy exposure.
  • At least 1 measurable lesion that can be reproducibly measured in 2 dimensions
  • Previous chemotherapy and hormone therapy (excluding physiologic replacement) must be completed at least 4 weeks or 4 half-lives, whichever is longer, prior to administration of DAY101.
  • Previous immunotherapy/ monoclonal antibody use must be completed at least 4 weeks or 4 half lives, whichever is longer prior to administration of DAY101.
  • Previous MEK or BRAF inhibitors must be completed at least 7 days prior to the administration of DAY101.
  • Focal or cranial spinal irradiation to the target lesion (whether as treatment or palliation) must be completed at least 6 months prior to administration of DAY101 to address the possibility of pseudoprogression. If pseudoprogression is definitively ruled out with tissue sampling (biopsy or repeat surgery), the patient may enroll after completion of radiation therapy at time of defined progression (and not wait 6 months) as long as patient meets other eligibility requirements.
  • All associated toxicities from previous therapies must be resolved to ≤ Grade 1 or considered baseline prior to administration of DAY101.
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling [e.g., United States Protection and Investigations (USPI), Summary of Product Characteristics (SmPC), etc,]) after the last dose of study drug, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
  • Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  • Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
  • Patient must be able to swallow pills whole.
  • Patient, parent, or legal guardian must be able to understand and be willing to provide informed consent.
  • Thyroid function tests must be consistent with stable thyroid function. Patients on a stable dose of thyroid replacement therapy for a suggested minimum of 3 weeks before Cycle 1, Day 1 are eligible.
  • Left ventricular ejection fraction (LVEF) of 50% or greater, as measured by echocardiogram (ECHO) or multiple gated acquisition (MUGA) scan, within 28 days before the first dose of DAY101
  • Inclusion of Women, Minorities, and Other Underrepresented Populations: This protocol is open to males and females of all races. See inclusion criteria above regarding specific eligibility requirements for female and male patients of child-bearing or child-fathering potential, respectively.
  • Exclusion Criteria: Patients with any of the following characteristics will NOT be eligible:
  • Patients with clinical progression but without radiographically recurrent or radiographically progressive disease.
  • Patients with NF1
  • History of any major disease that might interfere with safe protocol participation, as determined by the investigator
  • Patients with a history or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO), or ophthalmopathy present at baseline that would be considered a risk factor for CSR or RVO
  • --- Patients with history of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) or Steven Johnson Syndrome in the setting of prior MEK or BRAF inhibitor exposure
  • Laboratory values:
  • Absolute neutrophil count (ANC) ≤ 1000/μL
  • Platelet count ≤ 75,000/μL (transfusion independent)
  • Hemoglobin < 9 g/dL (hemoglobin may be supported by transfusion, erythropoietin, or other approved hematopoietic growth factors)
  • Serum bilirubin ≥ 1.5 × upper limit of normal (ULN) or ³ 2 ´ ULN if patient is known to have Gilbert's Disease as the only underlying hepatic disorder
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.5 × ULN. AST and ALT ≥ 5 × ULN for patients with liver metastasis
  • Serum creatinine ≥ 2.0 mg/dL
  • Current enrollment in any other investigational treatment study
  • Evidence of current uncontrolled cardiovascular conditions, including but not limited to clinically significant cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction, within the past 6 months
  • Active hepatitis or human immunodeficiency virus infection
  • Active bacterial or viral infection
  • Female patients who are pregnant or currently breastfeeding. Female patients of childbearing potential must have a negative serum pregnancy test prior to enrollment.
  • Major surgery within 28 days of Day 1 (does not include central venous access or shunts)
  • Inability to comply with study requirements
  • Refractory nausea and vomiting, malabsorption, or significant bowel or stomach resection that would preclude adequate absorption of DAY101
  • Treatment with any of the strong CYP2C inducers within 14 days before the first dose of DAY101 (see Appendix H).
  • Treatment with gemfibrozil (strong CYP2C8 inhibitor) within 14 days before the first dose of DAY101.
  • Other unspecified reasons that, in the opinion of the investigator, make the patient unsuitable for enrollment.
  • Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.

Who cannot join

None listed.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Massacusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institite

    Boston, Massachusetts, 02215

  • University of Florida

    Gainesville, Florida, 32610

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Children's Minnesota

    Minneapolis, Minnesota, 55404

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of Utah

    Salt Lake City, Utah, 84113

  • University of California, San Diego

    San Diego, California, 92123

  • University of California, San Francisco

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University in St. Louis

    St Louis, Missouri, 63110

  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase I Study of Tovorafenib/DAY101 (Formerly TAK-580, MLN2480) for Children With Low-Grade Gliomas and Other RAS/RAF/MEK/ERK Pathway Activated Tumors

This research study is studying a drug Tovorafenib/DAY101 (formerly TAK-580, MLN2480) as a possible treatment a low-grade glioma that has not responded to other treatments.

The name of the study drug involved in this study is:

  • Tovorafenib/DAY101 (formerly TAK-580, MLN2480)
Read the detailed description

This is a Phase I clinical trial. A Phase I clinical trial tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved DAY101 as a treatment for any disease.

This is the first time that DAY101 will be given to children. There is limited experience with DAY101 in humans.

The purpose of this study is to test the safety DAY101 in children and adolescent participants with brain tumors. The investigators want to find out what effects, good and/or bad, it has on participants and the participant's brain tumor, and find the dose of DAY101 that is tolerated by participants without too many side effects to use in Phase II of the study.

Research in the laboratory has shown that DAY101 may have activity against cancer cells. DAY101 belongs to a group of drugs called type II BRAF inhibitors. BRAF abnormalities are found in cancer cells. There are no type II BRAF inhibitors approved by the FDA for humans at the time of this study's start. DAY101 functions by binding the mutant BRAF molecule and causing a conformation change in the molecule thereby blocking the signal that tells the tumor cell to divide.

Being tested
DAY101
Keywords
low-grade glioma

What participants receive

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

  • DAY101Drug

    Also called MLN2480, TAK-580

    28 day cycle, oral, once per week

Study groups in NCT03429803
Study groupRoleWhat they receive
DAY101 (formerly TAK-580, MLN2480) BSA </= 1.5m^2ExperimentalPhase I Part B BSA </= 1.5m^2 * Patients (< 25 years) with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1 * Study treatment cycle lasts 28 days, oral, once a week
Receives: Drug: DAY101
DAY101 (formerly TAK-580, MLN2480) BSA > 1.5m^2ExperimentalPhase I Part B BSA > 1.5m^2 * Patients (< 25 years) with radiographically recurrent or radiographically progressive non-hematologic malignancies (Central Nervous System (CNS) or solid tumors) associated with activation of the RAS/RAF/MEK/ERK pathway will be eligible with the exception of patients with NF1 * Study treatment cycle lasts 28 days, oral, once a week
Receives: Drug: DAY101

What is being measured

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

  1. Dose Limiting Toxicity (DLT)

    A DLT is defined as an AE assessed as at least possibly related to the study medication, which occurs during Cycle 1 (typically 28 days following the first dose of DAY101)

    Measured: Greater and equal 28 days

Secondary outcomes (4)

  1. Blood samples for DAY101 concentration measurements (i.e. pharmacokinetic measures)

    measurement of phosphorylated ERK in peripheral blood mononuclear cells, will be performed on all patients in the phase I component of the trial

    Measured: cycle 1 day 1 1-4 hours post dose; cycle 1 day 3-6 random level; cycle 2 day 1 pre-dose; cycle 3 day 1 random level; end of therapy or at time of toxicity requiring patient be taken off study or dose held; time of surgery if applicable)

  2. Best Overall Response

    Pediatric patients (>1 year and <25 years of age). each evaluable patient will be classified as either a responder (complete response, partial response, or stable disease) or a non-responder (<stable disease)

    Measured: 48 Weeks

  3. Number of participants with adverse events

    Frequency of adverse events (AEs) with once weekly administration of DAY101

    Measured: 48 Weeks

  4. Number of participants with serious adverse events

    Frequency of serious adverse events (SAEs) with once weekly administration of DAY101

    Measured: 48 weeks

Timeline

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

  1. First posted12 Feb 2018
  2. Study start27 Feb 2018
  3. Primary completion31 Dec 2025
  4. Study completion31 Dec 2025

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03429803
Sponsor's protocol ID
17-589
Other IDs
P50CA165962, PNOC014
Status last verified
Feb 2026
First submitted
9 Jan 2018
Last updated
19 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: o 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 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 1 study testing DAY101 in people with Low-grade Glioma, run by Karen D. Wright, MD at 15 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 56 inclusion and 0 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: finished, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose Limiting Toxicity (DLT) (time frame: Greater and equal 28 days). 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 NCT03429803.

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 19 Feb 2026.

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