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:
Information provided by:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00808899
First received: December 11, 2008
Last updated: May 25, 2010
Last verified: May 2010
  Purpose

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.


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

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Complete Response Plus Partial Response [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
    The objective was to measure the efficacy and feasability of Temsirolimus and Irinotecan as measured by the objective response rate and toxicity rate.


Enrollment: 4
Study Start Date: December 2008
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  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: NCT00808899

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Wayne L Furman, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Wayne L. Furman, MD, St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00808899     History of Changes
Other Study ID Numbers: NB2008
Study First Received: December 11, 2008
Results First Received: April 19, 2010
Last Updated: May 25, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
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
Etoposide phosphate
Irinotecan
Cisplatin
Cyclophosphamide
Doxorubicin
Etoposide
Tretinoin
Sirolimus
Topotecan
Everolimus
Isotretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 22, 2014