Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Childhood Hepatocellular Carcinoma; Childhood Teratoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Childhood High-grade Cerebral Astrocytoma; Recurrent Childhood Liver Cancer; Childhood Central Nervous System Germ Cell Tumor; Recurrent Renal Cell Cancer; Recurrent Childhood Cerebral Astrocytoma; Childhood Hepatoblastoma; Recurrent Childhood Brain Stem Glioma; Recurrent Colon Cancer; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Nasopharyngeal Cancer; Childhood Malignant Ovarian Germ Cell Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Rectal Cancer; Childhood Malignant Testicular Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Childhood Extragonadal Germ Cell Tumor

Treatments: Drug: oxaliplatin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00091182

CDR0000384560

NCI-2012-01815

U10CA098543 (U.S. NIH Grant/Contract)

COG-ADVL0421

ADVL0421

Details and patient eligibility

About

This phase II trial is studying how well oxaliplatin works in treating young patients with recurrent solid tumors that have not responded to previous treatment. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die.

Full description

OBJECTIVES:

I. Determine the response rate in children with recurrent or refractory solid tumors treated with oxaliplatin.

II. Determine the cumulative toxicity of this drug in these patients. III. Determine the pharmacokinetic profile of this drug in these patients. IV. Determine time to progression and overall survival of patients treated with this drug.

V. Correlate the extent of oxaliplatin exposure with response in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type.

Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Enrollment: 180 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed* solid tumor, including any of the following:

  • Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET)

  • Osteosarcoma

  • Rhabdomyosarcoma

  • Neuroblastoma

  • High-grade astrocytoma

  • Low-grade astrocytoma

  • Glioblastoma multiforme

  • Ependymoma

  • Hepatoblastoma

  • Germ cell tumors of any site

  • Rare tumors of interest, including any of the following:

    • Soft tissue sarcoma
    • Hepatocellular carcinoma
    • Childhood/adolescent colorectal carcinoma
    • Childhood/adolescent renal cell carcinoma
    • Childhood/adolescent adrenocortical carcinoma
    • Childhood/adolescent nasopharyngeal carcinoma

• Recurrent disease OR refractory to conventional therapy

• Measurable disease by clinical exam, CT scan, MRI, or positron emission tomography

• Performance status - Karnofsky 50-100% (for patients over age 10)

• Performance status - Lansky 50-100% (for patients age 10 and under)

• At least 8 weeks

• Absolute neutrophil count ≥ 1,000/mm^3*

• Platelet count ≥ 75,000/mm^3* (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL* (RBC transfusions allowed)

• Granulocytopenia, anemia, and/or thrombocytopenia due to bone marrow metastases or extensive prior radiotherapy allowed provided the above hematological criteria are met

• Bilirubin ≤ 3 mg/dL

• Creatinine based on age as follows:

  • ≤ .8 mg/dL (for patients age 5 and under)
  • ≤ 1.0 mg/dL (for patients age 6 to 10)
  • ≤ 1.2 mg/dL (for patients age 11 to 15)
  • ≤1.5 mg/dL (for patients age 16 to 21)

• Creatinine clearance or radioisotope glomerular filtration rate > 20 mL/min

• No uncontrolled seizure disorder

• No uncontrolled infection

• CNS toxicity ≤ grade 2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Recovered from prior immunotherapy

• At least 7 days since prior anticancer biologic therapy

• More than 1 week since prior growth factors

• At least 6 months since prior allogeneic stem cell transplantation

  • No evidence of active graft-vs-host disease

• No concurrent immunomodulating agents

• Recovered from prior chemotherapy

• No prior oxaliplatin

• Prior carboplatin or cisplatin allowed

• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)

• No other concurrent anticancer chemotherapy

• Concurrent dexamethasone for CNS tumors allowed provided patient has been on a stable or decreasing dose for ≥ 1 week before study entry

• Recovered from prior radiotherapy

• At least 2 weeks since prior local palliative radiotherapy (small port)

• At least 6 months since prior craniospinal 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

• Concurrent radiotherapy to localized painful lesions allowed provided ≥ 1 measurable lesion is not irradiated

• No other concurrent investigational agents

• No other concurrent anticancer agents

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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180 participants in 1 patient group

Arm I

Experimental group

Description:

Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: oxaliplatin