Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

NCT ID: NCT00101270

Last Updated: 2013-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31

Brief Summary

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

Detailed Description

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (irinotecan hydrochloride, 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.

Group Type: EXPERIMENTAL

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

oxaliplatin

Intervention Type: DRUG

Given IV

Interventions

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

oxaliplatin

Given IV

Intervention Type: DRUG

Other Intervention Names

Campto; Camptosar; CPT-11; irinotecan; U-101440E; 1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP

Eligibility Criteria

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)

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa McGregor

Role: PRINCIPAL_INVESTIGATOR

COG Phase I Consortium

Locations

COG Phase I Consortium

Arcadia, California, United States

Countries

United States

Other Identifiers

ADVL0415

Identifier Type: -

Identifier Source: secondary_id

CDR0000401518

Identifier Type: -

Identifier Source: secondary_id

COG-ADVL0415

Identifier Type: -

Identifier Source: secondary_id

U01CA097452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01819

Identifier Type: -

Identifier Source: org_study_id