A Phase I Study of Oxaliplatin (NSC# 266046, IND #57004) and Irinotecan in Pediatric Patients With Refractory Solid Tumors and Lymphomas

Inclusion Criteria:

- Histologically confirmed refractory malignant solid tumor or lymphoma

- Intrinsic brain stem tumors and optic pathway tumors do not require histologic
verification

- No known curative therapy or therapy proven to prolong survival with an acceptable
quality of life exists

- Measurable or evaluable disease

- Evaluable disease is defined as a tumor that cannot be measured using a ruler or
calipers, but can be assessed to determine disease progression or complete
response, such as any of the following:

- Positive lesions on metaiodobenzylguanidine (MIBG) or bone scan

- Metastatic bone marrow disease

- Elevated tumor markers

- Presence of a malignant pleural effusion

- No leukemia

- Performance status - Karnofsky 50-100% (for patients > 10 years of age)

- Performance status - Lansky 50-100% (for patients ≤ 10 years of age)

- Not specified

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT ≤ 5 times ULN

- Albumin ≥ 2 g/dL

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min

- Creatinine based on age as follows:

- No greater than 0.8 mg/dL (for patients age 5 and under)

- No greater than 1.0 mg/dL (for patients age 6 to 10)

- No greater than 1.2 mg/dL (for patients age 11 to 15)

- No greater than 1.5 mg/dL (for patients age 16 and over)

- No arrhythmia on EKG

- No evidence of dyspnea at rest

- No exercise intolerance

- Pulse oximetry > 94% on room air and no evidence of pulmonary fibrosis by chest
radiograph* or CT scan

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- Weight ≥ 10 kg

- Neurologic deficits relatively stable for ≥ 1 week before study entry (patients with
CNS tumors only)

- No electrolyte (e.g., sodium, potassium, bicarbonate, calcium, magnesium, and
phosphate) abnormality ≥ grade 2 (electrolyte supplementation allowed)

- No uncontrolled infection

- No history of life-threatening allergy to camptothecin derivatives or platinum agents

- No sensory or motor peripheral neuropathy ≥ grade 2

- No elevation of amylase or lipase ≥ grade 2

- Able to tolerate enteral medications (e.g., cefixime, cefpodoxime, or loperamide)

- Recovered from all prior immunotherapy

- At least 7 days since prior hematopoietic growth factors

- At least 7 days since prior antineoplastic biologic therapy

- Prior stem cell transplantation or rescue without total-body irradiation (TBI)
allowed provided ≥ 3 months have elapsed and there is no evidence of active
graft-versus-host disease

- No concurrent immunotherapy

- No concurrent biologic therapy

- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for
nitrosoureas) and recovered

- No prior oxaliplatin

- No other concurrent chemotherapy

- Concurrent steroids allowed provided dose has been stable for ≥ 7 days before study
entry

- See Biologic therapy

- Recovered from all prior radiotherapy

- At least 2 weeks since prior local palliative small port radiotherapy

- At least 6 months since prior TBI

- At least 6 months since prior craniospinal, whole spinal, or whole lung/abdominal
radiotherapy

- At least 6 months since prior radiotherapy to ≥ 50 % of the pelvis

- At least 6 weeks since other prior substantial radiotherapy to the bone marrow

- No concurrent radiotherapy

- No other concurrent investigational drugs

- No other concurrent anticancer therapy

- No concurrent cephalosporin antibiotics

- No concurrent use of any of the following:

- Phenytoin

- Carbamazepine

- Oxcarbazepine

- Barbiturates

- Rifampin

- Phenobarbital

- Azole antifungal agents

- Aprepitant

- Hypericum perforatum (St. John's wort)