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

NCT00808899 | Terminated Phase 2 Results

• 1 other identifier: NB2008
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuroblastoma

Keywords

Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Plus Partial Response

  The objective was to measure the efficacy and feasability of Temsirolimus and Irinotecan as measured by the objective response rate and toxicity rate.

  10 years

Study Arms (1)

1

EXPERIMENTAL

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; 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

Interventions

Temsirolimus DRUG

Temsirolimus

1

Irinotecan DRUG

Irinotecan

1

Surgical Resection of Primary Tumor PROCEDURE

Surgical Resection of Primary Tumor

1

Cyclophosphamide DRUG

Cyclophosphamide

1

Doxorubicin DRUG

Doxorubicin

1

Etoposide DRUG

Etoposide

1

Cisplatin DRUG

Cisplatin

1

Topotecan DRUG

Topotecan

1

PBSC PROCEDURE

Peripheral Blood Stem Cell Harvest

1

Radiation Therapy RADIATION

Radiation Therapy

1

13-cis-retinoic acid DRUG

13-cis-retinoic acid

1

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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
• Age \> 18 mo (\> 547 days) with unfavorable pathology, regardless of MYCN status
• INSS stage 4 and:
• MYCN amplification, regardless of age or additional biologic features
• Age \> 18 months (\> 547 days) regardless of biologic features
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Neuroblastoma

Interventions

temsirolimus; Irinotecan; Cyclophosphamide; Doxorubicin; Etoposide; Cisplatin; Topotecan; Radiotherapy; Isotretinoin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Biological Factors

Limitations and Caveats

NB2008 was closed because of the publication of a new standard of care for treating high-risk neuroblastoma.At the time of closure, NB2008 had enrolled only 4 patients, which was an insufficient number of patients to answer the primary objective.

Results Point of Contact

• Title: Wayne L. Furman
• Organization: St. Jude Children's Research Hospital

info@stjude.org

1-866-278-5833

Study Officials

• Wayne L Furman, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2008
• First Posted: December 16, 2008
• Study Start: December 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: May 30, 2017
• Results First Posted: May 20, 2010

Record last verified: 2010-05

Locations

US (1)