ADVL1722, A Phase 2, multicenter, open-label study to assess safety and preliminary activity of eribulin mesylate in pediatric subjects with relapsed/refractory rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) and Ewing sarcoma (EWS)
Study ID: STU 122017-012
This is a Phase 2, multicenter, open-label study to conduct a preliminary assessment of the safety and activity of eribulin mesylate in pediatric subjects with relapsed/refractory RMS, nRSTS, or eWS.
1. Age: >= 12 months to < 18 years old at the time of informed consent. 2. Diagnosis: Histologically confirmed rhabdomyosarcoma (RMS), non-rhabdomysosarcoma soft tissue sarcoma (NRSTS) (Grade 2 or 3) or Ewing sarcoma (EWS) which is relapsed or refractory (failed front line therapy). 3. The presence of measurable disease meeting the following criteria: * At least 1 lesion of >= 1.0 cm in the longest diameter for a non-lymph node or >= 1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using computed tomography (CT)/magnetic resonance imaging (MRI). * Lesions that have had radiotherapy must show subsequent radiographic evidence of increase in size by at least 20% to be deemed a target lesion. 4. Therapeutic options: Subject[Single Quote]s 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. 5. Performance level: Performance score >= 50%. Karnofsky (for subjects > 16 years of age) or Lansky (for subjects <= 16 years of age). 6. Subjects must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to study drug administration. If, after the required time frame, the numerical eligibility criteria are met, eg, blood count criteria, the subject is considered to have recovered adequately: * Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea). * Anticancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. * Antibodies: 3 half-lives must have elapsed from infusion of last dose of antibody (including checkpoint inhibitors), and toxicity related to prior antibody therapy must be recovered to Grade <= 1. * Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (eg, Neulasta) or 7 days for a short-acting growth factor. For agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. * Interleukins, interferons, and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferons or cytokines (other than hematopoietic growth factors). * Stem cell infusions (with or without total body irradiation [TBI]): >= 84 days. * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD). * Autologous stem cell infusion including boost infusion: >= 42 days. * Cellular therapy: >= 42 days after the completion of any type of cellular therapy (eg, modified T-cells, natural killer cells, dendritic cells, etc). * Radiation therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT, >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis, >= 42 days if other substantial BM radiation. * Radiopharmaceutical therapy (eg, radiolabeled antibody, 131I-metaiodobenzylguanidine): >= 42 days after systemically administered radiopharmaceutical therapy. 7. Adequate bone marrow function, defined as: * ANC >= 1.0 x 10^9/L * Platelet count >= 100 x 10^9/L (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to study drug administration) * Hemoglobin at least 8.0 g/dL at Baseline (blood transfusions are allowed during the screening period to correct hemoglobin values less than 8.0 g/dL) As blood transfusions are permitted to meet the hemoglobin criteria, subjects requiring transfusion must not be known to be refractory to red blood cell or platelet transfusions. 8. Adequate renal function, defined as: * A serum creatinine based on age/gender as listed in the protocol, derived from the Schwartz formula for estimating glomerular filtration rate (GFR) * Or creatinine clearance or radioisotope GFR >= 50 mL/min/1.73 m2 based on a 12 or 24 hour urine creatinine collection. 9. Adequate liver function, defined as: a. Bilirubin (sum of conjugated + unconjugated) <= 1.5 x upper limit of normal (ULN) for age b. ALT (alanine aminotransferase) <= 110 U/L. For the purpose of this study, the ULN for ALT is 45 U/L. c. Serum albumin >= 2 g/dL 10. Informed consent: All subjects and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Subjects must be willing to comply with all aspects of the protocol.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
CHILDRENS ONCOLOGY GROUP OPERATIONS CTR
Bones and Joints; Soft Tissue