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

Information source: St. Jude Children's Research Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Neuroblastoma

Intervention: Temsirolimus (Drug); Irinotecan (Drug); Surgical Resection of Primary Tumor (Procedure); Cyclophosphamide (Drug); Doxorubicin (Drug); Etoposide (Drug); Cisplatin (Drug); Topotecan (Drug); PBSC (Procedure); Radiation Therapy (Radiation); 13-cis-retinoic acid (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: St. Jude Children's Research Hospital

Official(s) and/or principal investigator(s):
Wayne L Furman, MD, Principal Investigator, Affiliation: St. Jude Children's Research Hospital

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.

Clinical Details

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

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

Primary outcome: Complete Response Plus Partial Response

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

Minimum age: N/A. Maximum age: 18 Years. Gender(s): Both.

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).

Locations and Contacts

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Additional Information

Starting date: December 2008
Last updated: May 25, 2010

Page last updated: August 23, 2015

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