Neuroblastoma Protocol 2008: Therapy for Children With Advanced Stage High Risk Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: Temsirolimus; Irinotecan; Surgical Resection of Primary Tumor; Cyclophosphamide; Doxorubicin; Etoposide; Cisplatin; Topotecan; PBSC; Radiation Therapy; 13-cis-retinoic acid
Intervention description: Temsirolimus; Irinotecan; Surgical Resection of Primary Tumor; Cyclophosphamide; Doxorubicin; Etoposide; Cisplatin; Topotecan; Peripheral Blood Stem Cell Harvest; Radiation Therapy; 13-cis-retinoic acid
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Irinotecan; Etoposide; Topotecan; Temsirolimus; Tretinoin; Isotretinoin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Neuroblastoma

Summary:

      A Phase II study of temsirolimus in combination with standard chemotherapy (irinotecan;
      cyclophosphamide, doxorubicin and etoposide (CAE); cisplatin and etoposide (HiPE) and
      topotecan (TPT) followed by and additional six courses of induction chemotherapy and then
      intensification with autologous hematopoietic stem cell transplantation. The first five
      courses of induction chemotherapy will also evaluate the feasibility of combining weekly
      temsirolimus with these standard chemotherapy combinations. This will be followed by 16
      months of oral maintenance therapy with eight months of 13-cis-retinoic acid and then eight
      months of oral topotecan.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients <18 years old with newly diagnosed, advanced stage, high-risk neuroblastoma
             defined as one of the following:

               -  Children < 1 yo with International Neuroblastoma Staging System (INSS) stage 2a,
                  2b, 3, 4 or 4S disease and MYCN amplification (>10 copies, or greater than
                  four-fold increase in MYCN signal as compared to reference signal)

               -  INSS 2a or 2b disease and MYCN amplification, regardless of age or additional
                  biologic features

               -  INSS stage 3 and:

                    1. MYCN amplification (>10 copies, or greater than four-fold increase in MYCN
                       signal as compared to reference signal, regardless of age or additional
                       biologic features

                    2. Age > 18 mo (> 547 days) with unfavorable pathology, regardless of MYCN
                       status

               -  INSS stage 4 and:

                    1. MYCN amplification, regardless of age or additional biologic features

                    2. Age > 18 months (> 547 days) regardless of biologic features

                    3. Age 12 - 18 months (365 - 547 days) with any of the following three
                       unfavorable biologic features (MYCN amplification, unfavorable pathology
                       and/or DNA index =1) or any biologic feature that is indeterminant/unknown

               -  Children less than or equal to 365 days initially diagnosed with: INSS stage 1,
                  2, 4S who progressed to a stage 4 without interval chemotherapy.

          -  Histologic proof of neuroblastoma or positive bone marrow for tumor cells with
             increased urine catecholamines.

          -  Adequate renal and hepatic function (serum creatinine <3 x upper limit of normal for
             age, (AST) aspartate aminotransferase < 3 x upper limit of normal).

          -  No prior therapy, unless an emergency situation requires local tumor treatment
             (discuss with PI)

          -  Written, informed consent according to institutional guidelines

        Exclusion Criteria:

          -  Any evidence, as judged by the investigator, of severe or uncontrolled systemic
             disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal
             disease).

          -  Pregnant or breast feeding (women of child-bearing potential).

          -  Children with INSS 4 disease, age <12 months with all 3 favorable biologic features
             (non-amplified MYCN, favorable pathology and DNA index >1).