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

Primary Purpose

Neuroblastoma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Temsirolimus

Irinotecan

Surgical Resection of Primary Tumor

Cyclophosphamide

Doxorubicin

Etoposide

Cisplatin

Topotecan

PBSC

Radiation Therapy

13-cis-retinoic acid

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring Neuroblastoma

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00808899

First Posted

December 11, 2008

Last Updated

April 24, 2017

Sponsor

St. Jude Children's Research Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00808899

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2010

Overall Recruitment Status

Terminated

Why Stopped

Voluntarily closed and terminated by the PI due to lack of feasibility

Study Start Date

December 2008 (undefined)

Primary Completion Date

July 2009 (Actual)

Study Completion Date

July 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuroblastoma

Keywords

Neuroblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Temsirolimus

Intervention Description

Temsirolimus

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Intervention Description

Irinotecan

Intervention Type

Procedure

Intervention Name(s)

Surgical Resection of Primary Tumor

Intervention Description

Surgical Resection of Primary Tumor

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Cyclophosphamide

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Description

Doxorubicin

Intervention Type

Drug

Intervention Name(s)

Etoposide

Intervention Description

Etoposide

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cisplatin

Intervention Type

Drug

Intervention Name(s)

Topotecan

Intervention Description

Topotecan

Intervention Type

Procedure

Intervention Name(s)

PBSC

Intervention Description

Peripheral Blood Stem Cell Harvest

Intervention Type

Radiation

Intervention Name(s)

Radiation Therapy

Intervention Description

Radiation Therapy

Intervention Type

Drug

Intervention Name(s)

13-cis-retinoic acid

Intervention Description

13-cis-retinoic acid

Primary Outcome Measure Information:

Title

Complete Response Plus Partial Response

Description

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

Time Frame

10 years

10. Eligibility

Sex

All

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: 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 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Wayne L Furman, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.stjude.org

Description

Related Info

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

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