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

Inclusion Criteria:

• Age: Patients must be > 1 year of age and ≤ 25 years of age at time of initiation ofprotocol therapy.

• Diagnosis: Patients have a histologically or radiographically confirmed relapsed orrefractory solid tumor.

• Disease Status: Patients must have evaluable disease.

• Patients may have CNS metastases at study entry, if they are previously treated orstable (defined by not requiring initation or increased steroids for 7 days).

• Performance Level: Karnofsky ≥ 50% for patients >16 years old, and Lansky ≥ 50 forpatients 1-16 years old. (Appendix I)

• Prior Therapy: Patients may have received prior therapy including single-agentirinotecan or temozolomide. Patients may not have previously been treated withcombination therapy of irinotecan and temozolomide.

• Patients must be fully recovered from the acute toxic effects of all priorchemotherapy, immunotherapy, or radiotherapy prior to entering this study.

1. Hematopoietic growth factor: At least 7 days must have elapsed since the lastadministration 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 ifgiven total body irradiation, craniospinal irradiation.

3. Autologous or Allogenic Stem Cell Transplant: Complete resolution of graftversus host disease and no current need for immunosuppressive medication.Greater than 3 months must have elapsed since engraftment and no longerrequiring 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 toobtaining laboratory result)

• Adequate Renal Function: a. Creatinine clearance or glomerular filtration rate ≥ 70ml/min/1.73m2 (calculatedor measured as appropriate for age and level of concern by treating MD)

• 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 fatalhepatic failure, temozolomide should not be administered if total bilirubin is >2.0 mg/dl or SGPT(ALT)> 3 x ULN.

Informed Consent: All patients ≥ 18 years of age must sign a written informed consent. For patients < 18 years old, the patient's parents or legal guardians must sign a written informed consent, unless the patient is an emancipated minor. Childhood Assent, when age appropriate as per institutional guidelines, should be signed by the participating patient. Consent may be obtained virtually, as per institutional guidelines.

Exclusion Criteria:

• 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 offetal and teratogenic adverse events as seen in animal/human studies.

• Concomitant Medications:

• Growth factor: Growth factors that support platelet or white cell number of functionmust not have been administered within the past 7 days.

• Investigational Drugs: Patients who are currently receiving another investigationaldrug. (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, oreribuin

2. Allergy to cephalosporins, without a reasonably available antibioticalternative

• Infection: Patients who have uncontrolled infection, positive blood cultures withinthe past 48 hours, or receiving treatment for Clostridium difficile infection.