A Phase Ib Trial of Eribulin in Combination with Irinotecan and Temozolamide in Children with Relapsed or Refractory Solid Tumors

Eligibility Criteria

• * Age: Patients must be \> 1 year of age and ≤ 25 years of age at time of initiation of protocol therapy.
• * Diagnosis: Patients have a histologically or radiographically confirmed relapsed or refractory solid tumor.
• * Disease Status: Patients must have evaluable disease.
• * Patients may have CNS metastases at study entry, if they are previously treated or stable (defined by not requiring initation or increased steroids for 7 days).
• * Performance Level: Karnofsky ≥ 50% for patients \>16 years old, and Lansky ≥ 50 for patients 1-16 years old. (Appendix I)
• * Prior Therapy: Patients may have received prior therapy including single-agent irinotecan or temozolomide. Patients may not have previously been treated with combination therapy of irinotecan and temozolomide.
• * Patients must be fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• 1. Hematopoietic growth factor: At least 7 days must have elapsed since the last administration of filgrastim, or 14 days since administration of pegfilgrastim.
• 2. XRT: At least 7 days since the last dose of local palliative radiation therapy. Greater than 6 months must have elapsed since the last day of treatment if given total body irradiation, craniospinal irradiation.
• 3. Autologous or Allogenic Stem Cell Transplant: Complete resolution of graft versus host disease and no current need for immunosuppressive medication. Greater than 3 months must have elapsed since engraftment and no longer requiring transfusion of platelets or injection of colony stimulating factors.
• * Organ Function Requirements
• * Bone Marrow Function:
• 1. Peripheral absolute neutrophil count (ANC) ≥ 750/µL
• 2. Platelet count ≥ 75,000/µL (no platelet transfusion within 7 days prior to obtaining laboratory result)
• * Adequate Renal Function:
• * Adequate Liver Function:
• 1. Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age
• 2. SGPT (ALT) ≤ 3 x ULN
• 3. Serum albumin ≥ 2gm/dL Due to the risk of hepatic injury, including fatal hepatic failure, temozolomide should not be administered if total bilirubin is \>2.0 mg/dl or SGPT(ALT)\> 3 x ULN.
• * Significant organ dysfunction, not meeting inclusion criteria.
• * Pediatric subjects who are considered wards of some entity
• * Pregnancy or Breast-Feeding
• * Pregnant or breast-feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
• * Concomitant Medications:
• * Growth factor: Growth factors that support platelet or white cell number of function must not have been administered within the past 7 days.
• * Investigational Drugs: Patients who are currently receiving another investigational drug. (Please refer to Prior Therapy, section 2.1.5)
• * Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents. (Please refer to Prior Therapy, section 2.1.5.1)
• * Medication Allergy:
• 1. Allergy or intolerance to agents on this protocol: irinotecan, temozolomide, or eribuin
• 2. Allergy to cephalosporins, without a reasonably available antibiotic alternative
• * Infection: Patients who have uncontrolled infection, positive blood cultures within the past 48 hours, or receiving treatment for Clostridium difficile infection.