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

Phase 1

Terminated

• Conditions: Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma
• Interventions: Drug: oxaliplatin; Drug: etoposide

• Registration Number: NCT00101205
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2004-11
• Study First Submitted: 2005-01-07
• Study First Submitted QC: 2005-01-07
• Study First Posted: 2005-01-10
• Primary Completion: 2012-01
• Status Verified: 2013-04
• Last Update Submitted: 2014-02-21
• Last Update Posted: 2014-02-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	oxaliplatin	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.
Arm I	etoposide	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.

Primary Outcome Measures

Name	Time	Method
MTD of the combination of oxaliplatin and etoposide assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0	21 days
MTD of the addition of ifosfamide to the combination of oxaliplatin and etoposide assessed by CTCAE version 3.0	21 days

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States