Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: irinotecan hydrochloride; temozolomide
Intervention description: Given IV; Given IV
Intervention MeSH terms: Irinotecan; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: recurrent neuroblastoma

Summary:

      RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving irinotecan together with
      temozolomide works in treating young patients with recurrent neuroblastoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed neuroblastoma AND/OR demonstration of tumor cells in the bone
             marrow with increased urinary catecholamines at initial diagnosis

               -  Patients with elevated catecholamines only are not eligible

          -  Meets 1 of the following criteria:

               -  Recurrent disease following aggressive, multidrug, frontline chemotherapy,
                  defined as chemotherapy given with ≥ 2 agents, including an alkylating agent and
                  a platinum-containing compound

               -  Resistant/refractory disease during aggressive, multidrug, frontline chemotherapy

          -  Must meet 1 of the following criteria for documentation of disease:

               -  Unidimensionally measurable tumor ≥ 20 mm by MRI (Magnetic Resonance Imaging), CT
                  scan (Computed Tomography), or x-ray OR ≥ 10 mm by spiral CT scan within 4 weeks
                  prior to study entry

                    -  Patients with residual stable tumor upon completion of frontline therapy
                       must undergo biopsy to document presence of a viable neuroblastoma

                    -  If the measurable target lesion was previously radiated, a biopsy must be
                       performed ≥ 4 weeks after radiation was completed AND the biopsy must
                       demonstrate viable neuroblastoma

               -  MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical) with positive
                  uptake at ≥ 1 site within 4 weeks prior to study entry

                    -  Patients with residual stable MIBG-positive lesions upon completion of
                       frontline therapy must undergo biopsy to document presence of viable
                       neuroblastoma

                    -  If the patient has only 1 MIBG-positive lesion, and that lesion was
                       previously radiated, a biopsy must be performed ≥ 4 weeks after radiation
                       was completed AND the biopsy must demonstrate viable neuroblastoma

               -  Bone marrow with tumor cells on routine morphology (not by neuron-specific
                  enolase staining only) of bilateral aspirate and/or biopsy on 1 bone marrow
                  sample within 2 weeks prior to study entry

          -  No extensive marrow disease

          -  No myelodysplastic syndrome

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky
             PS 50-100% (for patients ≤ 16 years of age)

          -  Life expectancy ≥ 8 weeks

          -  Absolute neutrophil count ≥ 750/mm^3

          -  Platelet count ≥ 75,000/mm^3 (transfusion independent)

          -  Hemoglobin ≥ 8.5 mg/dL (transfusion allowed)

          -  Creatinine adjusted according to age as follows:

               -  No greater than 0.4 mg/dL (≤ 5 months)

               -  No greater than 0.5 mg/dL (6 months -11 months)

               -  No greater than 0.6 mg/dL (1 year-23 months)

               -  No greater than 0.8 mg/dL (2 years-5 years)

               -  No greater than 1.0 mg/dL (6 years-9 years)

               -  No greater than 1.2 mg/dL (10 years-12 years)

               -  No greater than 1.4 mg/dL (13 years and over [female])

               -  No greater than 1.5 mg/dL (13 years to 15 years [male])

               -  No greater than 1.7 mg/dL (16 years and over [male]) OR

          -  Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

          -  ALT < 2.5 times ULN for age

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Seizure disorder allowed provided seizures are well controlled on non-EIAC medication

          -  No active diarrhea or uncontrolled infection

          -  No other malignancy, including secondary malignancy

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Prior front-line therapy (e.g., surgery, chemotherapy, immunotherapy, radiotherapy, or
             retinoids) allowed

          -  Recovered from prior therapy

          -  More than 4 weeks since prior radiation therapy to the site of any lesion that will be
             identified as a target lesion to measure tumor response

          -  At least 2 weeks since prior myelosuppressive therapy (4 weeks for nitrosourea)

          -  At least 1 week since prior therapy with an antineoplastic biologic agent or retinoid

          -  At least 1 week since prior growth factors

          -  At least 1 week since prior and no other concurrent anticancer agents

          -  At least 1 week since prior and no concurrent enzyme-inducing anticonvulsants (EIAC),
             including phenytoin, phenobarbital, valproic acid, or carbamazepine

               -  Concurrent gabapentin or levetiracetam allowed

          -  Concurrent palliative radiation therapy to sites not used to measure tumor response
             allowed

          -  No prior allogeneic stem cell transplantation (SCT)

               -  Prior autologous SCT allowed

          -  No prior second-line chemotherapy for relapsed or refractory disease

          -  No concurrent immunomodulating agents

               -  Concurrent steroids for transfusion/infusion reactions or for treatment of edema
                  associated with CNS lesions allowed