I5B-MC-JGDN, A Phase 1, Open-Label, Dose-Escalation Study of Olaratumab as a Single Agent and in combination with Doxorubicin, Vincristine/Irinotecan, or High-Dose Ifosfamide in Pediatric Patients with Relapsed or Refractory Solid Tumors
Study ID: STU 012016-066
Study JGDn is a multicenter, dose-escalation, open-label Phase 1 pediatric safety clinical trial with 2 distinct components, Part a and Part B. Part a will consist of approximately 12 evaluable pediatric patients treated for 1 cycle (21 days) of olaratumab monotherapy at 15 mg/kg on Day 1 and Day 8. if the patient does not experience a dose-limiting toxicity (DLT) in the first cycle of monotherapy, or meet any other criteria for discontinuation, the patient will then receive olaratumab (15 mg/kg) plus one of 3 standard chemotherapy regimens (doxorubicin or vincristine/irinotecan or high-dose ifosfamide per investigator discretion). Part B will consist of approximately 12 evaluable pediatric patients treated for 1 cycle of olaratumab monotherapy at 20 mg/kg on Day 1 and Day 8. if the patient does not experience a DLT in the first cycle of monotherapy, or meet any other criteria for discontinuation, the patient will then receive olaratumab (20 mg/kg) in combination with any of the 3 chemotherapy regimens in Part a that have successfully passed the DLT criteria described above for Part a (doxorubicin or vincristine/irinotecan or high-dose ifosfamide per investigator discretion). Treatment will continue until disease progression or other discontinuation criteria are met.
Patients may be included in the study if they meet all of the following criteria during screening prior to first dose of study drug.  The patient must have histological or cytological evidence of a diagnosis of solid tumor, excluding lymphomas and melanoma, but including central nervous system (CNS) tumors, that is relapsed or refractory, not be amenable to curative treatment, and for whom chemotherapy with doxorubin, vincristine/irinotecan, or ifosfamide is deemed appropriate by the investigator. For patients with CNS tumors, neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment.  The patient has the presence of measurable and/or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria In Solid Tumors (RECIST Version 1.1). Response Assessment in Neuro-Oncology (RANO) Criteria or Macdonald Criteria should be used for CNS tumors.  The patient is <18 years of age at the time of first dose of study drug.  The patient, or patient[Single Quote]s parent/guardian, has given written informed consent and authorization for release of health information for research prior to any study-specific procedures being performed.  The patient has a Lansky (<16 years of age; Lansky et al. 1987) or Karnofsky (>=16 years of age; Karnofsky et al. 1948) performance score of at least 50.  The patient has adequate hematologic, organ, and coagulation function <=2 weeks (14 days) prior to first dose of study drug: - Absolute neutrophil count (ANC) >/= 750/mm3. Granulocyte colony-stimulating factor (G-CSF) cannot be administered <=1 week (7 days) prior to first dose of study drug. Pegfilgrastin cannot be administered <=2 weeks (14 days) prior to first dose of study drug. - Platelets >/= 75,000/mm3. Platelet transfusion to meet this enrollment criterion is not allowed within the preceding 5 days of first dose of study drug. - Hemoglobin >/= 8 g/dL. Transfusions with packed red blood cells is allowed. - Total bilirubin (sum of conjugated + unconjugated) <= 1.5 X upper limit of normal (ULN) for age. - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3.0 times ULN. If the liver has tumor involvement, AST and ALT equaling <= 5.0 times ULN are acceptable. - Serum creatinine is based on age/gender as listed in the protocol. - The patient has an adequate coagulation function as defined by International Normalized Ratio <=1.5 or prothrombin time <=1.5 x ULN, and partial thromboplastin time <=1.5 x ULN if not receiving anticoagulation therapy. For patients receiving anticoagulants, exceptions to these coagulation parameters are allowed if they are within the intended or expected range for their therapeutic use. Patients must have no history of active bleeding (defined as within 14 days of first dose of study drug) or pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or known esophageal varices).  Female patients of child-bearing potential must have a negative serum pregnancy test within 7 days prior to Cycle 1 Day 1.  Both female and male patients of child-bearing potential must agree to use highly effective contraceptive precautions during the trial and up to 3 months following the last dose of study drug, as appropriate. A highly effective method of birth control is defined as one that results in a low failure rate (that is, <1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner.  Patients must have fully recovered from the acute toxic effects of all prior anticancer therapies or must adhere to post-treatment conditions as follows: - Myelosuppressive chemotherapy: at least 21 days after the last dose of myelosuppressive chemotherapy (or 42 days if prior nitrosourea) - Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (for example, Neulasta(RegisteredTM)) or 7 days for 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. The duration of this interval must be discussed with Lilly clinical research physician or clinical research scientist (CRP/CRS). - Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent - Antibody therapy: at least 3 half-lives after the last treatment - Radiation: 14 days since local palliative radiation therapy (RT) (small port); 150 days if patient has had prior total body irradiation (TBI), craniospinal RT, or 50% or greater pelvic radiation; 42 days for other substantial radiation (such as metaiodobenzylguanidine therapy) - Stem Cell Infusion without total body irradiation (TBI): at least 84 days must have elapsed after transplant or stem cell infusion - Corticosteroids: for patients with CNS lesions, the dose of corticosteroids should be stable for at least 1 week.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
ELI LILLY AND COMPANY
Bones and Joints; Brain and Nervous System; Other Urinary; Ovary; Prostate; Soft Tissue