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

NCT ID: NCT00808899

Last Updated: 2017-05-30

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-31

Study Completion Date

2009-07-31

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Neuroblastoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Temsirolimus

Intervention Type DRUG

Temsirolimus

Irinotecan

Intervention Type DRUG

Irinotecan

Surgical Resection of Primary Tumor

Intervention Type PROCEDURE

Surgical Resection of Primary Tumor

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide

Doxorubicin

Intervention Type DRUG

Doxorubicin

Etoposide

Intervention Type DRUG

Etoposide

Cisplatin

Intervention Type DRUG

Cisplatin

Topotecan

Intervention Type DRUG

Topotecan

PBSC

Intervention Type PROCEDURE

Peripheral Blood Stem Cell Harvest

Radiation Therapy

Intervention Type RADIATION

Radiation Therapy

13-cis-retinoic acid

Intervention Type DRUG

13-cis-retinoic acid

Interventions

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Temsirolimus

Temsirolimus

Intervention Type DRUG

Irinotecan

Irinotecan

Intervention Type DRUG

Surgical Resection of Primary Tumor

Surgical Resection of Primary Tumor

Intervention Type PROCEDURE

Cyclophosphamide

Cyclophosphamide

Intervention Type DRUG

Doxorubicin

Doxorubicin

Intervention Type DRUG

Etoposide

Etoposide

Intervention Type DRUG

Cisplatin

Cisplatin

Intervention Type DRUG

Topotecan

Topotecan

Intervention Type DRUG

PBSC

Peripheral Blood Stem Cell Harvest

Intervention Type PROCEDURE

Radiation Therapy

Radiation Therapy

Intervention Type RADIATION

13-cis-retinoic acid

13-cis-retinoic acid

Intervention Type DRUG

Eligibility Criteria

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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).
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wayne L Furman, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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NB2008

Identifier Type: -

Identifier Source: org_study_id

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