Clinical trial NCT00004068: Irinotecan Followed by Radiation Therapy and Temozolomide in Treating Children With Newly Diagnosed Brain Tumor
Official title: Treatment of Newly Diagnosed High-Grade Gliomas in Patients Ages Greater Than or Equal to 3 and Less Than or Equal to 21 Years With a Phase II Irinotecan Window Followed by Radiation Therapy and Temozolomide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: childhood high-grade cerebral astrocytoma
childhood high-grade cerebellar astrocytoma
childhood oligodendroglioma
untreated childhood brain stem glioma
untreated childhood cerebellar astrocytoma
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-08
Enrollment: 53
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of irinotecan followed by radiation therapy and temozolomide in treating children who have newly diagnosed brain tumor.

Detailed description: OBJECTIVES:

* Evaluate the efficacy of adjuvant irinotecan in children with newly diagnosed high grade gliomas, brain stem glioma, or high risk grade II astrocytomas in terms of complete and partial response rate in patients with postoperative measurable disease, and in terms of the rate of freedom from recurrence in patients with no postoperative measurable disease.
* Determine the 3 year overall and progression free survival rates in this patient population when treated with adjuvant irinotecan followed by radiotherapy and temozolomide.
* Assess the hematopoietic toxicity of temozolomide following local radiotherapy in this patient population.

OUTLINE: Patients receive postoperative irinotecan IV over 60 minutes daily for 5 days on weeks 1-2. Treatment repeats every 3 weeks for 2 courses. Following completion of irinotecan and if appropriate, patients may undergo a second surgical resection.

Within 2 weeks following completion of chemotherapy or within 4 weeks of following a second resection, patients receive image guided external beam radiotherapy 5 days per week for 6 weeks. Patients with residual tumor less than 3.5 cm in maximal diameter may undergo boost radiosurgery.

At 4 weeks following completion of radiotherapy, patients receive oral temozolomide for 5 days. Treatment repeats every 3 weeks for 6 courses.

Patients are followed every 3 months for 2 years, then every 4 months for 3 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed newly diagnosed brain tumors

  * Grade III or IV disease:

    * Glioblastoma multiforme
    * Anaplastic astrocytoma
    * Anaplastic oligodendroglioma
    * Anaplastic pleomorphic xanthoastrocytoma
    * Anaplastic or malignant oligoastrocytoma
    * Gemistocytic astrocytoma
    * Malignant glioma
  * Grade II glial tumors in unfavorable locations (i.e., imaging evidence of gliomatosis cerebri and/or bithalamic involvement)
  * Diffuse pontine gliomas with greater than 2/3 involvement of the pon

PATIENT CHARACTERISTICS:

Age:

* 3 to 21

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 2,500/mm\^3
* Platelet count greater than 100,000/mm\^3
* Hemoglobin greater than 8.0 g/dL

Hepatic:

* Bilirubin no greater than 2.5 mg/dL
* SGOT/SGPT less than 5 times normal

Renal:

* Creatinine no greater than 2.0 mg/dL

Other:

* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Prior corticosteroids allowed

Radiotherapy:

* No prior radiotherapy

Surgery:

* No more than 28 days since prior definitive surgery for brain tumor

Other:

* Concurrent anticonvulsants allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Memphis
country: United States
facility: Saint Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Amar Gajjar, MD
role: STUDY_CHAIR
References:
citation: Broniscer A, Chintagumpala M, Fouladi M, Krasin MJ, Kocak M, Bowers DC, Iacono LC, Merchant TE, Stewart CF, Houghton PJ, Kun LE, Ledet D, Gajjar A. Temozolomide after radiotherapy for newly diagnosed high-grade glioma and unfavorable low-grade glioma in children. J Neurooncol. 2006 Feb;76(3):313-9. doi: 10.1007/s11060-005-7409-5.
citation: Broniscer A, Iacono L, Chintagumpala M, Fouladi M, Wallace D, Bowers DC, Stewart C, Krasin MJ, Gajjar A. Role of temozolomide after radiotherapy for newly diagnosed diffuse brainstem glioma in children: results of a multiinstitutional study (SJHG-98). Cancer. 2005 Jan 1;103(1):133-9. doi: 10.1002/cncr.20741.
citation: Broniscer A, Chintagumpala M, Bowers D, et al.: Upfront protracted irinotecan (CPT-11) followed by radiotherapy (RT) and temozolomide (TMZ) in the treatment of children with newly diagnosed high-grade glioma (HGG) and unfavorable low-grade glioma (LGG): results of a multi-institutional study (SJHG-98). [Abstract] Neuro-Oncology 6 (4): TP-01, 385, 2004.