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Brain TumorPhase 1NCT04334863

WP1066 in Children With Refractory and Progressive or Recurrent Malignant Brain Tumors

A Phase 1 study testing WP1066 in people with Brain Tumor and Medulloblastoma, run by Emory University at 1 site 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

In this Phase I clinical study, the investigators plan to offer investigational treatment with the novel JAK2/STAT3 inhibitor WP1066 (Moleculin Biotech, Inc.) to pediatric patients with any progressive or recurrent malignant brain tumor that is refractory to standard treatment and is without known cure. Read more about this study

Who is it for?
Ages 3 to 25 years
Conditions the study is for
Brain Tumor, Medulloblastoma, Brain Metastases
What is being tested?
WP1066
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
4 May 2020to 3 Feb 2023
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 3 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must have histologically confirmed progressive medulloblastoma, malignant glioma or any other recurrent/progressive malignant brain tumor, for which curative measures do not exist. Primary spinal tumors are eligible. DIPG and DMG H3K27M do not require histological confirmation.
  • Patients with DIPG and DMG with H3K27M who are post-radiation but have not exhibited tumor progression are also eligible.
  • Patients must have previously undergone standard-of-care treatment including surgery, radiation, and/or first line adjuvant chemotherapy prior to the experimental treatment (WP1066).
  • Patients must have recovered from the acute treatment related toxicities (defined as < grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. There is no upper limit to the number of prior therapies that is allowed.
  • Age > 3 to 25 years.
  • Karnofsky or Lansky Performance Scale score > 60%.
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  • Patients must have normal organ and marrow function as defined below:
  • Absolute neutrophil count> 1,000/mcL
  • Platelets> 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT)< 5 x (<10 x if taking steroids) institutional upper limit of normal
  • creatinine within normal institutional limits for age OR creatinine clearance> 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • PT/PTT< 1.5 x normal institutional standard
  • Patients with stable seizures (e.g., no seizures for ≥ 14 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.
  • Signed informed written consent obtained from patient if 18 years of age or older, or from guardian/legal representative if patient is less than 18 years of age

Who cannot join

  • Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks prior to study enrollment or at least six (6) weeks if prior nitrosourea.
  • Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. Agents with prolonged half-lives: At least three half-lives must have elapsed prior to enrollment.
  • Immunotherapy: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses. etc.) at least 42 days prior to enrollment.
  • Radiation: Patients must have had their last fraction of:
  • Craniospinal irradiation ≥ 3 months prior to enrollment.
  • Other substantial bone marrow irradiation ≥ 6 weeks prior to enrollment
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  • Local palliative XRT (small port) ≥2 weeks.
  • Stem Cell Transplant: Patient must be ≥ 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment.
  • Surgery Patients must be fully recovered from all acute effects of prior surgical intervention.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to WP1066.
  • The enzymatic metabolism profile of WP1066 is unknown. Patients who are receiving drugs that significantly interact with the CYP450 enzyme(s) are ineligible. However, if they are switched to other medications with a 2-week washout window, they will be eligible. Patients are also excluded if they have been exposed within 7 days of planned first study treatment day to medications that are predominantly CYP2D6, 2C9 or 2C19 substrates, strong inhibitors or inducers, and sensitive substrates of CYP3A4 with narrow therapeutic range.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • No single lesion can be larger than 5 cm in maximal diameter. There may not be clinically significant midline shift or hydrocephalus.
  • The effects of WP1066 on the developing human fetus are unknown. Pregnant women are excluded from this study because WP1066 could potentially be teratogenic or have abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with WP1066, breastfeeding should be discontinued if the mother is treated with WP1066. Female subjects of childbearing potential should be willing to use 2 methods of birth control prior to study entry, during the study, and for 2 months after the last dose of the study drug or be surgically sterile. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of WP1066 administration.
  • HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with WP1066.
  • The potential for further hemorrhaging with the use of WP1066 is unknown. It will be at the PIs discretion to enroll a patient who has a small, asymptomatic brain hemorrhage, but patients who have had symptomatic hemorrhages will be excluded.
  • Patients requiring escalation of the corticosteroid dose will be excluded, but patients receiving a stable or decreasing dose for at least one week prior to registration will be eligible.
  • The cardiac toxicities of WP1066 are unknown. Thus, patients who have a mean QTc interval >450 ms at baseline will be excluded. Concomitant use of agents that prolong the QT interval will be avoided.
  • Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs will be excluded.
  • The use of medical cannabis and CBD oil is prohibited during the first 2 cycles of this protocol. Patients must be off cannabis oil for 3 days prior to enrollment

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Healthcare of Atlanta (CHOA)

    Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: A Phase I Study of WP1066 in Children With Refractory and Progressive or Recurrent Malignant Brain Tumors (AflacST1901)

In this Phase I clinical study, the investigators plan to offer investigational treatment with the novel JAK2/STAT3 inhibitor WP1066 (Moleculin Biotech, Inc.) to pediatric patients with any progressive or recurrent malignant brain tumor that is refractory to standard treatment and is without known cure.

Read the detailed description

The goal of this clinical research study is to find the highest tolerable dose of WP1066 that can be given to pediatric patients with recurrent (has returned after treatment) cancerous brain tumors or melanoma that has gotten worse and spread to the brain. The safety of this drug will also be studied.

WP1066 is designed to target the STAT3 pathway in cancer cells, which makes these cells divide, increases new blood vessels to the tumor, causes the cancer cells to move throughout the body and brain, and avoids them being detected by the immune system. Targeting this pathway may cause the immune system to kill the cancer cells. The investigators will administer five escalating doses of WP1066, starting at lowest dose currently found to be safe and tolerable in adults.

WP1066 is not FDA approved or commercially available. It is currently being used for research purposes only.

Up to 36 participants will be enrolled in this study. All will take part at Children's Healthcare of Atlanta (CHOA).

Being tested
WP1066
Keywords
Brain Tumor
Medical subject headings
Brain Neoplasms, Medulloblastoma

What participants receive

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

  • WP1066Drug

    Also called STAT3 Inhibitor WP1066

    WP1066 is an analogue of caffeic acid that is a potent inhibitor of p-STAT3.

    It will be taken by mouth 2 times per day on Monday, Wednesday, and Friday of Weeks 1 and 2 of each 28-day cycle.

Study groups in NCT04334863
Study groupRoleWhat they receive
WP1066ExperimentalThere will be 5 groups based on the enrollment timing. The first group of participants will receive the lowest dose level of WP1066. Each subject within a group will receive an assigned dose of the investigational drug. The dose levels are 4, 6, 8 and 16 mg/kg of the investigational drug given twice a day. The first group will receive the lowest dose level, 4mg/kg twice a day, and subsequent groups will escalate to the next higher dose level. All groups will be treated identically, except for the dose of drug administered, with the liquid formulation of the drug.
Receives: Drug: WP1066

What is being measured

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

  1. Maximum tolerated dose (MTD) of WP1066

    Maximum tolerated dose (MTD) of WP1066 in pediatric patients with recurrent or refractory and progressive malignant brain tumors for which there is no known treatment with clinical benefit.

    Maximum tolerated dose (MTD) is determined as the dose level at which 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) with at least 2 patients experiencing DLT at the next higher dose level. DLT is defined as an adverse event or an abnormal laboratory value assessed as being at least possibly related to the investigational agent that occurs during the first 28 days after administration of the first dose of WP1066.

    Measured: 28 Days post-intervention

  2. Change in safety and tolerability of WP1066: Maximum tolerated dose (MTD) and Dose limiting toxicities (DLT)

    The trial will investigate the maximum tolerated dose (MTD) and record the dose limiting toxicities (DLTs) at least possibly related to the investigational drug, as well as all toxicities related or unrelated that occur. MTD is defined as the dose level at which 0/6 or 1/6 subjects experience a DLT with at least 2 subjects experiencing DLT at the next higher dose level. A minimum of 6 subjects must be treated at the MTD. DLT is defined as a graded adverse event or abnormal lab value at least possibly related to the investigational drug that occurred within 28 days after the first dose of the drug was administered. All toxicities will be recorded and graded throughout the study.

    Measured: Up to 2 months after the last study drug dose

Secondary outcomes (13)

  1. Pharmacokinetic of WP1066: Peak plasma concentration (Cmax)

    Cmax is the observed maximum plasma concentration following drug administration. Individual plasma concentration-time data for WP1066 will be used to generate pharmacokinetic parameter estimates using both compartmental and non-compartmental methods.

    Measured: Days 1, 2, 14, and 15 of course 1

  2. Pharmacokinetic of WP1066: Time to peak concentration (Tmax)

    Tmax is the time to reach maximum plasma concentration after single dose administration. Individual plasma concentration-time data for WP1066 will be used to generate pharmacokinetic parameter estimates using both compartmental and non-compartmental methods.

    Measured: Days 1, 2, 14, and 15 of course 1

  3. Pharmacokinetic of WP1066: Area Under the Plasma Concentration-time Curve from time zero to 24 hours (AUC0-24)

    AUC0-24 is the area under the plasma concentration-time curve from time zero to 24 hours after the start of WP1066 and will be calculated using the linear trapezoidal. Individual plasma concentration-time data for WP1066 will be used to generate pharmacokinetic parameter estimates using both compartmental and non-compartmental methods.

    Measured: Days 1, 2, 14, and 15 of course 1

  4. Pharmacokinetic analysis of WP1066: Clearance from plasma (CL) following drug administration

    CL is the systemic (or total body) clearance from plasma following WP1066 administration. It will be determined by dose/AUC. Individual plasma concentration-time data for WP1066 will be used to generate pharmacokinetic parameter estimates using both compartmental and non-compartmental methods.

    Measured: Days 1, 2, 14, and 15 of course 1

  5. Pharmacokinetic analysis of WP1066: Elimination half life (t1/2)

    Elimination half-life (t1/2) will be calculated by 0.693/k. Individual plasma concentration-time data for WP1066 will be used to generate pharmacokinetic parameter estimates using both compartmental and non-compartmental methods.

    Measured: Days 1, 2, 14, and 15 of course 1

  6. Pharmacokinetic analysis of WP1066: Apparent volume of distribution

    Apparent volume of distribution will be calculated by Cl/k. Individual plasma concentration-time data for WP1066 will be used to generate pharmacokinetic parameter estimates using both compartmental and non-compartmental methods.

    Measured: Days 1, 2, 14, and 15 of course 1

  7. Pharmacokinetic analysis of WP1066: change in accumulation ratio of WP1066

    Accumulation ratio of WP1066 will be calculated as the ratio of AUC0-24 on cycle 1 Day 1 vs Cycle 1 fourth dose. Individual plasma concentration-time data for WP1066 will be used to generate pharmacokinetic parameter estimates using both compartmental and non-compartmental methods.

    Measured: Day 1 of cycle 1 (each cycle is 28 days) and Day 7 of cycle 1

  8. Pharmacodynamic analysis of WP1066: level of activated Stat3

    Activated Stat3 is a transcription factor which in humans is encoded by the STAT3 gene. It is a member of the STAT protein family. The level of activated Stat3 (phospho-Stat3) will be measured in the peripheral blood mononuclear cells (PBMCs), the type of immune cells present in the blood, and the immune cytokines in the serum of subjects pre and post administration of the investigational drug.

    Measured: Hours 0, 4, 24 of Day 1 and Hours 0, 4, 24 of Day 7

  9. Change in overall response rate (ORR) of WP1066 treatment

    Change in overall response rate (ORR) of WP1066 treatment for this pediatric study population in those with radiographically measurable disease.

    Measured: Up to 2 months after the last study drug dose

  10. Change in Immunological response

    If clinically indicated and as an optional procedure, biopsy or surgery specimens of the tumors will be obtained to determine the molecular expression of p-STAT3, Ki-67 and immunological characteristics of the tumors (Treg infiltration, co-stimulator molecule expression, etc.)

    Measured: Up to 2 months after the last study drug dose

  11. Time to radiographically assessed progression and/or response to treatment with WP1066.

    The subjects will undergo imaging at baseline and again within 30 days after obtaining the MRI that aroused the suspicion of progression, or an alternative imaging method can be employed, such as MRI with spectroscopy and/or perfusion, or positron emission tomography (PET).

    Measured: Up to 2 months post-intervention

  12. Change in progression-free survival (PFS)

    The PFS will be defined radiographically as a greater than 25% increase in tumor volume (in malignant glioma) on T1-weighted MRI scans compared with the MRI obtained within 4 weeks before enrollment.

    Estimated using Kaplan-Meier survival curves. Cox proportional hazards regression methodology may be used to assess the association between duration of response or survival and clinical and demographic characteristics of interest.

    Measured: Up to 2 months after the last study drug dose

  13. Change in overall survival (OS)

    Estimated using Kaplan-Meier survival curves. Cox proportional hazards regression methodology may be used to assess the association between duration of response or survival and clinical and demographic characteristics of interest.

    Measured: Up to 2 months after the last study drug dose

Timeline

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

  1. First posted6 Apr 2020
  2. Study start4 May 2020
  3. Primary completion3 Feb 2023
  4. Study completion3 Feb 2023

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
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04334863
Sponsor's protocol ID
IRB00113194
Status last verified
Feb 2023
First submitted
2 Apr 2020
Last updated
21 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Castellino RC, Mumme H, Franson A, Yu B, Robinson H, Dhodapkar K, Aguilera D, Schniederjan M, Keesari R, He Z, Bhasin M, Priebe W, Heimberger AB, MacDonald TJ. First-in-child phase I trial of p-STAT3 inhibitor WP1066 in pediatric brain tumor patients. JCI Insight. 2025 Dec 11;11(3):e194823. doi: 10.1172/jci.insight.194823. eCollection 2026 Feb 9.

    PubMed 41379553

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing WP1066 in people with Brain Tumor and Medulloblastoma, run by Emory University 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 15 inclusion and 20 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 21 Feb 2023. 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 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?

Maximum tolerated dose (MTD) of WP1066 (time frame: 28 Days post-intervention). 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 NCT04334863, which also lists 1 linked publication.

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 21 Feb 2023.

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