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Neuroblastoma Protocol 2008: Therapy for Children With Advanced Stage High Risk Neuroblastoma

This study has been terminated.
(Voluntarily closed and terminated by the PI due to lack of feasibility)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00808899
First Posted: December 16, 2008
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
December 11, 2008
December 16, 2008
April 19, 2010
May 20, 2010
May 30, 2017
December 2008
July 2009   (Final data collection date for primary outcome measure)
Complete Response Plus Partial Response [ Time Frame: 10 years ]
The objective was to measure the efficacy and feasability of Temsirolimus and Irinotecan as measured by the objective response rate and toxicity rate.
Temsirolimus and Irinotecan in Children With High-risk Neuroblastoma Followed by an Evaluation of the Feasibility of Combining Temsirolimus With Standard Induction Chemotherapy With Cyclophosphamide, Doxorubicin, Etoposide, Topotecan and Cisplatin. [ Time Frame: 10 years ]
Complete list of historical versions of study NCT00808899 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Neuroblastoma Protocol 2008: Therapy for Children With Advanced Stage High Risk Neuroblastoma
Neuroblastoma Protocol 2008: Therapy for Children With Advanced Stage High Risk Neuroblastoma
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.

All children will receive fixed doses of intravenous temsirolimus (50 mg/m2 weekly 6 times ) concomitantly with two courses of fixed dosages of irinotecan (20 mg/m2 intravenously daily 5 times ,2 days off, repeated daily 5 times .If these initial dosages are not tolerable then subsequent patients will be given a reduced dosage of temsirolimus (25 mg/m2 weekly 6 times) with 20 mg/m2 of irinotecan.If this dosage combination is not tolerable, the irinotecan dosage will be decreased to 15 mg/m2 .If this dosage combination is not tolerable then further enrollment to the initial six week treatment will be terminated.The second course of irinotecan will begin on day 22 and response will be determined after six weeks (two courses). Resection of primary tumor will be attempted after this initial therapy, whenever possible.

Following initial treatment children will undergo alternating courses of induction chemotherapy with cyclophosphamide, doxorubicin, etoposide, topotecan, and cisplatin (Block 2). The first cohort of 17 patients will receive Block 2 with temsirolimus (50mg/m2) for all three courses, weekly 2 times. If this is not tolerated subsequent patients will receive Block 2 chemotherapy with reduced dosages of temsirolimus (25mg/m2).

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Neuroblastoma
  • Drug: Temsirolimus
    Temsirolimus
  • Drug: Irinotecan
    Irinotecan
  • Procedure: Surgical Resection of Primary Tumor
    Surgical Resection of Primary Tumor
  • Drug: Cyclophosphamide
    Cyclophosphamide
  • Drug: Doxorubicin
    Doxorubicin
  • Drug: Etoposide
    Etoposide
  • Drug: Cisplatin
    Cisplatin
  • Drug: Topotecan
    Topotecan
  • Procedure: PBSC
    Peripheral Blood Stem Cell Harvest
  • Radiation: Radiation Therapy
    Radiation Therapy
  • Drug: 13-cis-retinoic acid
    13-cis-retinoic acid
Experimental: 1
Fixed doses of IV temsirolimus concomitantly with two courses of fixed dosages of irinotecan, 2 days off, repeated daily 5 times.If initial dosages are not tolerable, subsequent patients will be given a reduced dosage of temsirolimus with irinotecan.If this dosage combination is not tolerable,irinotecan dosage will be decreased.If this dosage combination is not tolerable.Further enrollment to initial six week treatment will be terminated.Second course of irinotecan will begin on day 22, response will be determined after six weeks. Resection of primary tumor will be attempted after initial therapy.Following initial treatment children will undergo alternating courses of induction chemotherapy with cyclophosphamide,doxorubicin,etoposide,topotecan, and cisplatin.First cohort of 17 patients will receive Block 2 with temsirolimus for all three courses, weekly 2 times.If this is not tolerated subsequent patients will receive Block 2 chemotherapy with reduced dosages of temsirolimus.
Interventions:
  • Drug: Temsirolimus
  • Drug: Irinotecan
  • Procedure: Surgical Resection of Primary Tumor
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Etoposide
  • Drug: Cisplatin
  • Drug: Topotecan
  • Procedure: PBSC
  • Radiation: Radiation Therapy
  • Drug: 13-cis-retinoic acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
July 2009
July 2009   (Final data collection date for primary outcome measure)

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).
Sexes Eligible for Study: All
up to 18 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00808899
NB2008
No
Not Provided
Not Provided
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
Not Provided
Principal Investigator: Wayne L Furman, MD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP