Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma

Official Title

Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients With Non-high-risk Neuroblastoma

Summary:

This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumour may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumour cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.

Trial Description

Primary Outcome:

  • OS (Strata 1-4)
  • EFS (Stratum 5)
Secondary Outcome:
  • Time to intervention or tumour progression
  • Type of intervention required
  • Site of progression
  • Pharmacokinetic (PK) profile of carboplatin and etoposide in patients with stage Ms disease, including peak concentration, area under the curve, clearance, volume of distribution, half-life, and mean residence time
  • Genomic profile of tumours
  • Histology of tumour specimens
  • Salvage rate (OS) of patients with tumour relapse or disease progression
  • Procedural complication rate
  • Rate of reduction in IDRF in L2 tumours
PRIMARY OBJECTIVES:
I. To eliminate therapy as the initial approach for infants < 12 months of age with small International Neuroblastoma Risk Group (INRG) stage L1 neuroblastoma while maintaining an overall survival (OS) of 99%. II. To eliminate therapy as the initial approach for non-high-risk patients < 18 months of age with localized neuroblastoma and favourable biology (histologic and genomic features) while maintaining an OS of 99%. III. To achieve a 3-year OS of > 81% for infants < 18 months of age with INRG stage Ms neuroblastoma using objective criteria for early initiation of a response-based treatment algorithm. SECONDARY OBJECTIVES:
I. To describe the time to intervention or tumour progression, type of intervention and site of progression for patients with localized neuroblastoma who experience progression after an initial period of observation. II. To characterize the pharmacokinetic profile of the chemotherapeutic agents carboplatin and etoposide in patients with stage Ms disease. III. To define the genomic profile of tumours from patients with non-high-risk neuroblastoma both at initial biopsy and at the time of subsequent biopsy or surgical resection. IV. To describe the histology of tumour specimens obtained at the time of subsequent biopsy or surgical resection. V. To determine the salvage rate (OS) of patients with tumour relapse or disease progression. VI. To determine the procedural complication rate (initial biopsy, resection [intraoperative and postoperative], subsequent biopsy) and correlate with the degree of surgical resection. VII. To determine the rate of reduction in image defined risk factors (IDRF) in L2 tumours following observation or chemotherapy. OUTLINE:

Patients are assigned to 1 of 3 treatment groups. GROUP A: Patients undergo clinical observation for 96 weeks in the absence disease progression. GROUP B: Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin intravenously (IV) over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a partial response (PR) or better is achieved, patients undergo clinical observation for 3 years. GROUP C: Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years. After completion of study treatment, patients are followed up annually for 5 years.

View this trial on ClinicalTrials.gov

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Resources

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