A Phase 1 Trial of LY2940680 in Pediatric Patients With Recurrent or Refractory Rhabdomyosarcoma or Medulloblastoma
- For Part A: Have a diagnosis of recurrent or refractory rhabdomyosarcoma or
medulloblastoma and have had histologic verification of malignancy at original
diagnosis or relapse.
- For Part B: Have a diagnosis of recurrent or refractory medulloblastoma and have had
histologic verification of malignancy at original diagnosis or relapse.
- Current disease state must be one for which there is no known curative therapy or
therapy proven to prolong survival with an acceptable quality of life.
- Karnofsky score must be at least 50% for participants >16 years of age, and Lansky
score must be at least 50% for participants 16 years of age or less. Participants who
are unable to walk because of paralysis, but who are in a wheelchair, will be
considered ambulatory for the purpose of assessing the performance score.
- Have fully recovered from the acute toxic effects of all prior anticancer
- Participants with solid tumors must not have received myelosuppressive
chemotherapy within 3 weeks of enrollment in this study (6 weeks, if previously
treated with nitrosourea).
- Hematopoietic growth factors: At least 14 days after the last dose of a
longacting growth factor (eg, Neulasta®) or 7 days for short-acting growth
- Biologic (antineoplastic agent): At least 7 days after the last dose of a
- Immunotherapy: At least 6 weeks since the completion of any type of
immunotherapy (eg, tumor vaccines).
- Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose
of a monoclonal antibody.
- Radiation therapy (XRT): ≥8 weeks for local irradiation to primary tumor;≥2
weeks prior to study entry for focal irradiation for symptomatic metastatic
sites; ≥3 months for craniospinal XRT, or ≥24 weeks if ≥50% radiation of pelvis;
minimum of 6 weeks must have elapsed if other substantial bone marrow radiation
has been received.
- Stem cell transplant: allowed if they have recovered from all acute toxicity and
adequate bone marrow reserve is demonstrated. At least 8 weeks must have elapsed
since autologous stem cell transplantation or ≥3 months for allogenic
transplantation. Participants must be off all immunosuppressive therapy and have
no evidence of active graft-versus-host disease.
- Have adequate organ function, including:
- Bone marrow: Peripheral absolute neutrophil count (ANC) ≥500/cubic millimeter
(mm^3) and platelet count ≥100,000/mm^3 (transfusion independent, defined as not
receiving platelet transfusions within a 7-day period prior to enrollment).
- Hepatic: Bilirubin (sum of conjugated + unconjugated)≤1.5 × upper limit of
normal (ULN) for age. Serum alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) ≤2.0 times ULN for age. Serum albumin ≥2 grams/deciliter
- Renal: Creatinine clearance or radioisotope glomerular filtration rate (GFR)
≥70 milliliters/minute/1.73 square meters (mL/min/1.73 m^2), or a serum
creatinine based on age/gender per the Schwartz formula for estimating GFR
utilizing child length and stature data published by the Centers for Disease
Control and Prevention (CDC).
- Neurologic: Participants with seizure disorders may be enrolled if receiving
nonenzyme-inducing anticonvulsants and if the symptoms are well controlled. They
must have a stable neurologic status for at least 1 week prior to enrollment in
- Must be able to swallow powder or a capsule.
- Have the presence of either measurable or nonmeasurable disease.
- Have received treatment within 21 days of the initial dose of study drug with an
experimental agent for noncancer indications that has not received regulatory
approval for any indication.
- Receiving corticosteroids and have not been on a stable or decreasing dose of
corticosteroid for the prior 7 days.
- Receiving enzyme-inducing anticonvulsants.
- Have serious preexisting medical conditions.
- Have current hematologic malignancies or acute or chronic leukemia.
- Have a known active fungal, bacterial, and/or known viral infection, including human
immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not
- Have a second primary malignancy that, in the judgment of the investigator and
sponsor, may affect the interpretation of results.
- Have ≥Grade 2 QT prolongation, that is, QTc interval of >480 milliseconds (msec) on
screening electrocardiography (ECG).