Neuroblastoma
Conditions
Keywords
Neuroblastoma
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).
Interventions
DRUGTemsirolimus
Temsirolimus
DRUGIrinotecan
Irinotecan
PROCEDURESurgical Resection of Primary Tumor
Surgical Resection of Primary Tumor
DRUGCyclophosphamide
Cyclophosphamide
DRUGDoxorubicin
Doxorubicin
DRUGEtoposide
Etoposide
DRUGCisplatin
Cisplatin
DRUGTopotecan
Topotecan
PROCEDUREPBSC
Peripheral Blood Stem Cell Harvest
RADIATIONRadiation Therapy
Radiation Therapy
13-cis-retinoic acid
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Plus Partial Response | 10 years | The objective was to measure the efficacy and feasability of Temsirolimus and Irinotecan as measured by the objective response rate and toxicity rate. |
Countries
United States
Participant flow
Recruitment details
Four patients were recruited from December, 2008 through April, 2009. The study was suspended July, 2009 because of the publication of a new standard of care in treatment for patients with high-risk neuroblastoma.
Participants by arm
| Arm | Count |
|---|---|
| Temsirolimus With Irinotecan Participants enrolled in the Temsiolimus and Irinotecan group were high-risk neuroblastoma patients. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 3 |
Baseline characteristics
| Characteristic | Temsirolimus With Irinotecan |
|---|---|
| Age, Continuous | 3.5 years STANDARD_DEVIATION 1.21 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
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.
Time frame: 10 years
Population: The population consisted of patients eligible for enrollment onto the NB2008 protocol.