Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 1

Conditions: Childhood Burkitt Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Grade III Lymphomatoid Granulomatosis; Small Intestine Lymphoma; Refractory Chronic Lymphocytic Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Angioimmunoblastic T-cell Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Noncutaneous Extranodal Lymphoma; Intraocular Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Childhood Diffuse Large Cell Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Childhood Large Cell Lymphoma; Hepatosplenic T-cell Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; Refractory Hairy Cell Leukemia; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Unspecified Childhood Solid Tumor, Protocol Specific; Peripheral T-cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma

Treatments: Drug: oxaliplatin; Drug: etoposide

Study type: Interventional

Funder types: NIH

Identifiers

NCT00101205

P30CA021765 (U.S. NIH Grant/Contract)

OXALET (Other Identifier)

CDR0000405828

NCI-2009-00075 (Registry Identifier)

6634 (Other Identifier)

Details and patient eligibility

About

This phase I trial is studying the side effects and best dose of oxaliplatin and etoposide in treating young patients with recurrent or refractory solid tumors or lymphomas. Drugs used in chemotherapy, such as oxaliplatin and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Oxaliplatin may also help etoposide work better by making cancer cells more sensitive to the drug. Giving oxaliplatin together with etoposide may kill more cancer cells.

Full description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of oxaliplatin and etoposide in pediatric patients with recurrent or refractory solid tumors or lymphoma.

II. Determine the dose-limiting toxic effects of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetic profile of this regimen in these patients. II. Correlate the extent of oxaliplatin and etoposide exposure with toxic effects and therapeutic effects of this regimen in these patients.

III. Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oxaliplatin IV over 2 hours on day 1 and etoposide IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin and etoposide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Enrollment: 40 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Life expectancy > 8 weeks
• Albumin > 2 g/dL
• Histologically confirmed diagnosis of 1 of the following: solid tumor; histologic verification not required for brainstem tumors or optic pathway tumors; lymphoma; recurrent or refractory to conventional therapy OR no known effective therapy exists; bone marrow involvement allowed
• Performance Status: Karnofsky >= 50 % (patients > 10 years of age) OR Lansky >= 50% (patients for =< 10 years of age)
• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 100,000/mm^3 (transfusion independent)
• Hemoglobin > 8 g/dL (transfusion allowed)
• ALT < 5.0 times ULN
• Creatinine normal OR glomerular filtration rate >= 80 mL/min/1.73 m^2
• Calcium normal (electrolyte supplements allowed)
• Echocardiogram and EKG normal
• Shortening fraction >= 27% OR ejection fraction > 50%
• No evidence of dyspnea at rest
• No exercise intolerance
• Pulse oximetry > 94% on room air
• Neurologic deficits due to CNS tumor must be relatively stable for >= 2 weeks before study entry
• Seizure disorder allowed provided well-controlled by non-enzyme-inducing anticonvulsants
• No peripheral neurotoxicity > grade 1
• Sodium, potassium, and magnesium normal (electrolyte supplements allowed)
• At least 1 week since prior biologic agents
• More than 1 week since prior growth factors
• More than 6 months since prior allogeneic peripheral blood stem cell transplantation AND no active graft-versus-host disease
• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
• More than 2 weeks since prior focal radiotherapy for symptomatic metastatic sites
• More than 6 weeks since prior substantial bone marrow radiotherapy
• More than 3 months since prior craniospinal (> 24 Gy), whole pelvis, or total-body radiotherapy
• Recovered from all prior therapy
• No concurrent enzyme-inducing anticonvulsants, including, but not limited to, the following: Barbiturates; Phenytoin; Carbamazepine

Exclusion criteria

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No history of life-threatening hypersensitivity to platinum-containing agents
• No prior oxaliplatin
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Arm I

Experimental group

Description:

Patients receive oxaliplatin IV over 2 hours on day 1 and etoposide IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: etoposide

Drug: oxaliplatin