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.
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
Up to 36 participants will be enrolled in this study. All will take part at Children's
Healthcare of Atlanta (CHOA).
- 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 does not require
- Patients must have previously undergone standard-of-care treatment including surgery,
radiation, and/or first line adjuvant chemotherapy prior to the experimental treatment
- 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%
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count > 1,000/mcL
- Platelets > 100,000/mc
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) < 5 x (<10 x if taking steroids) institutional upper limit of
- 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.
- 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 •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
- 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
- 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.