Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00311584
First received: April 5, 2006
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Drug: irinotecan hydrochloride
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Irinotecan + Temozolomide in Children With Recurrent Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Overall Response (Complete and Partial Response) [ Time Frame: up to 6 courses of therapy, or about 6 months ] [ Designated as safety issue: No ]
    The patient's best overall response obtained during Reporting Periods 1 and 2 will be scored as "best response". A patient will be considered evaluable for response if they have an event at any time or they complete at least two courses of Irinotecan/Temozolomide therapy. A responder is defined to be a patient who achieves a best overall response of CR (Complete Response), VGPR (Very Good Partial Response) or PR (Partial Response).


Enrollment: 59
Study Start Date: April 2006
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Disease measurable by CT or MRI scan (Irinotecan/Temozolomide)
Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • CPT-11
  • NSC #616348
Drug: temozolomide
Given IV
Other Names:
  • TEMODAR
  • NSC #362856
Experimental: Disease eval by bone marrow or MIBG (Irinotecan/Temozolomide)
Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • CPT-11
  • NSC #616348
Drug: temozolomide
Given IV
Other Names:
  • TEMODAR
  • NSC #362856

Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in pediatric patients with relapsed neuroblastoma (NB) treated with irinotecan hydrochloride and temozolomide.
  • Determine the toxicities associated with irinotecan and temozolomide in patients treated with this regimen.

Secondary

  • Evaluate the impact of p53 loss of function on response rate and event-free survival from start of relapse therapy.
  • Collect data for ongoing analyses of UGT1A1 polymorphisms in these patients.
  • Collect and bank serum and nucleic acid specimen to facilitate future biomarker studies.
  • Evaluate the feasibility of collecting blood samples on a group wide basis for assessment of changes in circulating markers of angiogenesis.
  • Assess, preliminarily, the effects of irinotecan hydrochloride and temozolomide on circulating markers of angiogenesis.

OUTLINE: This is a multicenter study.

Patients are stratified according to disease status (measurable disease [measured by conventional CT scan and/or MRI] vs evaluable disease [tumor detected by conventional morphologic analysis of bone marrow aspirate/biopsy AND/OR abnormal uptake at ≥ 1 site on MIBG scan]).

Patients receive irinotecan hydrochloride IV over 1 hour on days 1-5 and 8-12 and oral temozolomide on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00311584

  Show 128 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Rochelle Bagatell, MD University of Arizona
Study Chair: Cynthia S. Kretschmar, MD Floating Hospital for Children at Tufts - New England Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00311584     History of Changes
Other Study ID Numbers: ANBL0421, CDR0000465487, COG-ANBL0421
Study First Received: April 5, 2006
Results First Received: December 2, 2013
Last Updated: December 2, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Irinotecan
Camptothecin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014