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


Phase 1
1 Year
21 Years
Not Enrolling
Both
Childhood Burkitt Lymphoma, Childhood Central Nervous System Germ Cell Tumor, Childhood Diffuse Large Cell Lymphoma, Childhood Grade III Lymphomatoid Granulomatosis, Childhood Immunoblastic Large Cell Lymphoma, Recurrent Childhood Brain Stem Glioma, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Liver Cancer, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Malignant Germ Cell Tumor, Recurrent Childhood Medulloblastoma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor, Recurrent Childhood Visual Pathway Glioma, Recurrent Colon Cancer, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Melanoma, Recurrent Nasopharyngeal Cancer, Recurrent Neuroblastoma, Recurrent Osteosarcoma, Recurrent Wilms Tumor and Other Childhood Kidney Tumors, Recurrent/Refractory Childhood Hodgkin Lymphoma, Unspecified Childhood Solid Tumor, Protocol Specific

Thank you

Trial Information

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


PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of oxaliplatin when administered with irinotecan in
pediatric patients with refractory solid tumors or lymphomas.

II. Determine the toxic effects of this regimen in these patients. III. Determine the
pharmacokinetics of this regimen in these patients.

SECONDARY OBJECTIVES:

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

II. Correlate UGT and BCRP genotype with the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of oxaliplatin.

Patients receive oxaliplatin IV over 2 hours on days 1 and 8 and irinotecan IV over 1 hour
on days 1-5 and 8-12. Treatment repeats every 21 days for up to 17 courses in the absence of
disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin 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.


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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of oxaliplatin, defined as the maximum dose at which fewer than one-third of patients experience DLT

Outcome Description:

Graded using the NCI CTCAE version 3.0.

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Lisa McGregor

Investigator Role:

Principal Investigator

Investigator Affiliation:

COG Phase I Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01819

NCT ID:

NCT00101270

Start Date:

March 2005

Completion Date:

Related Keywords:

  • Childhood Burkitt Lymphoma
  • Childhood Central Nervous System Germ Cell Tumor
  • Childhood Diffuse Large Cell Lymphoma
  • Childhood Grade III Lymphomatoid Granulomatosis
  • Childhood Immunoblastic Large Cell Lymphoma
  • Recurrent Childhood Brain Stem Glioma
  • Recurrent Childhood Cerebellar Astrocytoma
  • Recurrent Childhood Cerebral Astrocytoma
  • Recurrent Childhood Ependymoma
  • Recurrent Childhood Grade III Lymphomatoid Granulomatosis
  • Recurrent Childhood Large Cell Lymphoma
  • Recurrent Childhood Liver Cancer
  • Recurrent Childhood Lymphoblastic Lymphoma
  • Recurrent Childhood Malignant Germ Cell Tumor
  • Recurrent Childhood Medulloblastoma
  • Recurrent Childhood Rhabdomyosarcoma
  • Recurrent Childhood Small Noncleaved Cell Lymphoma
  • Recurrent Childhood Soft Tissue Sarcoma
  • Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
  • Recurrent Childhood Visual Pathway Glioma
  • Recurrent Colon Cancer
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Melanoma
  • Recurrent Nasopharyngeal Cancer
  • Recurrent Neuroblastoma
  • Recurrent Osteosarcoma
  • Recurrent Wilms Tumor and Other Childhood Kidney Tumors
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Astrocytoma
  • Burkitt Lymphoma
  • Colonic Neoplasms
  • Ependymoma
  • Glioma
  • Hodgkin Disease
  • Kidney Neoplasms
  • Liver Neoplasms
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Medulloblastoma
  • Melanoma
  • Wilms Tumor
  • Neuroblastoma
  • Osteosarcoma
  • Rhabdomyosarcoma
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Nasopharyngeal Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Rhabdomyosarcoma, Embryonal
  • Sarcoma
  • Optic Nerve Glioma
  • Lymphoma, Extranodal NK-T-Cell
  • Neoplasms
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral

Name

Location

COG Phase I ConsortiumArcadia, California  91006-3776