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

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00808899
• Other study ID #: NB2008
• Status: Terminated
• Phase: Phase 2
• First received: December 11, 2008
• Last updated: May 25, 2010
• Start date: December 2008
• Est. completion date: July 2009

Study information

• Verified date: May 2010
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• Temsirolimus
Temsirolimus
• Irinotecan
Irinotecan

Procedure:
• Surgical Resection of Primary Tumor
Surgical Resection of Primary Tumor

Drug:
• Cyclophosphamide
Cyclophosphamide
• Doxorubicin
Doxorubicin
• Etoposide
Etoposide
• Cisplatin
Cisplatin
• Topotecan
Topotecan

Procedure:
• PBSC
Peripheral Blood Stem Cell Harvest

Radiation:
• Radiation Therapy
Radiation Therapy

Drug:
• 13-cis-retinoic acid
13-cis-retinoic acid

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes

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