Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors

Inclusion Criteria:

1. Patients must be 1 year of age to ≤ 30 years of age at the time of study entry.

2. Patients must have had histologic verification of a solid tumor or CNS tumor ateither original diagnosis or relapse.

3. Measurable or evaluable disease is not required for enrollment on thissafety/feasibility study.

4. Patient's current disease state must be one for which there is no known curativetherapy or therapy proven to prolong survival with an acceptable quality of life orfor which irinotecan and/or temozolomide are acceptable therapeutic options based onexisting standard of care available.

5. Karnofsky Performance Status ≥ 50% for patients > 16 years of age and LanskyPerformance Status ≥ 50 for patients ≤ 16 years of age. Patients who are unable towalk because of paralysis, but who are up in a wheelchair, will be consideredambulatory for the purpose of assessing the performance score.

6. Males or females of reproductive potential may not participate unless they haveagreed to use an effective contraception method during and for 30 days after studytreatment. (Abstinence is considered an acceptable method of effectivecontraception.)

7. Prior treatment with temozolomide, vincristine or irinotecan is allowed, althoughpatients must not have had disease progression while receiving either irinotecan,vincristine or temozolomide.

8. Patients must have recovered from the acute toxic effects of all prior chemotherapy,immunotherapy, or radiotherapy prior to entering this study, as described below:

9. Myelosuppressive chemotherapy: patients must not have received myelosuppressivechemotherapy within 21 days of first study treatment, but nitrosourea within 8weeks (42 days) of first study treatment

10. Anti-cancer agents not known to be myelosuppressive (e.g., not associated withdrops in platelet or neutrophil count): must not have received these therapieswithin 7 days of first study treatment, or at least 5 half-lives of the agent (whichever is longer)

11. Antibody therapy: At least 4 weeks must have elapsed since last antibody doseprior to first study treatment

12. Radiation therapy: At least two weeks must have elapsed since last localpalliative radiation (small port) prior to first study treatment. At least 6weeks must have elapsed if more substantial radiation was administered (e.g., >50% pelvis, craniospinal, whole body), or therapeutic radiolabeled 131I MIBGor other radiopharmaceutical therapy.

13. High-Dose Chemotherapy with Autologous Stem Cell Transplant/Rescue: At leasttwo months must have elapsed since receiving autologous hematopoietic stemcells prior to first study treatment. Patients who have had allogeneictransplants are ineligible.

14. Hematopoietic growth factors: must not have been received in the 14 days priorto first study treatment for a long-acting growth factor (e.g., pegfilgrastim),or 7 days prior to first study treatment for short-acting growth factor.

15. Peripheral absolute neutrophil count (ANC) ≥ 1,000/µL

16. Platelet count ≥100,000/µL (transfusion independent, defined as not receivingplatelet transfusions within a 7-day period prior to first study treatment)

17. Hemoglobin ≥ 8.0 gm/dL (may receive RBC transfusions) NOTE: Patients with metastatictumor in the bone marrow ARE eligible provided the above hematologic criteria aremet.

18. Creatinine clearance or radioisotope GFR ≥ 70mL/min/1.73 m2 or Serum creatininebased on age/gender as follows: Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

≥ 16 years 1.7 1.4 The threshold creatinine values in this Table were derived from the Schwartz formulafor estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child lengthand stature data published by the CDC.

13. Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) forage

14. SGPT (ALT) ≤ 5 x upper limit of normal (ULN) for age

15. Serum albumin ≥ 2 g/dL

Exclusion Criteria:

1. Patients with a history of severe allergic reaction (e.g., more than simple rash) todacarbazine or third-generation cephalosporins are ineligible.

2. Pregnant or breast-feeding women will not be entered on this study due to potentialrisks of fetal and teratogenic adverse events. A pregnancy test must be obtainedprior to starting chemotherapy in post-menarchal female patients.

3. Patients who are currently receiving investigational drugs, or who have received aninvestigational drug within the last 7 days prior to first study treatment, areineligible.

4. Patients who are currently receiving other anti-cancer agents are ineligible.

5. Patients taking strong inducers of CYP3A4, including but not limited tophenobarbital, phenytoin, carbamazepine, oxcarbazepine (Trileptal), rifampin,voriconazole, itraconazole, ketoconazole or other systemically-administered azoleantifungal drugs, aprepitant (Emend) or St. John's Wort, in the 2 weeks prior tofirst study treatment are ineligible.

6. Patients taking strong inhibitors of CYP3A4 or UGT1A1 in the 1 week prior to firststudy treatment are ineligible.

7. Patients must not be receiving medications known to inhibit platelet function orknown to selectively inhibit cyclooxygenase activity. Medicines in this class areexcluded, with the exception of acetaminophen.

8. Patients who have uncontrolled infections, require IV antibiotics at time ofenrollment, or who are currently receiving treatment for Clostridium difficileinfection are excluded.

9. Patients who in the opinion of the investigator may not be able to comply with thesafety monitoring requirements of the study are not eligible.