Clinical trial NCT00101205: Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma
Official title: A Phase I Trial of the Combination of Oxaliplatin (NSC 266046, IND 57004), Ifosfamide, and Etoposide in Recurrent or Refractory Pediatric Solid Tumors and Lymphomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Angioimmunoblastic T-cell Lymphoma
B-cell Childhood Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
Childhood Burkitt Lymphoma
Childhood Diffuse Large Cell Lymphoma
Childhood Grade III Lymphomatoid Granulomatosis
Childhood Immunoblastic Large Cell Lymphoma
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
T-cell Childhood Acute Lymphoblastic Leukemia
T-cell Large Granular Lymphocyte Leukemia
Unspecified Childhood Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-01-10
Enrollment: 40
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: MTD of the combination of oxaliplatin and etoposide assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
timeFrame: 21 days
measure: MTD of the addition of ifosfamide to the combination of oxaliplatin and etoposide assessed by CTCAE version 3.0
timeFrame: 21 days
Secondary outcomes:
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Lisa McGregor
role: PRINCIPAL_INVESTIGATOR
References: