Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma
This phase III trial is studying the side effects and how well giving combination chemotherapy together with autologous stem cell transplant and/or radiation therapy works in treating young patients with extraocular retinoblastoma. Giving chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and/or bone marrow and stored. More chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Radiation therapy uses high energy x-rays to kill tumor cells. Giving radiation therapy after combination chemotherapy and/or autologous stem cell transplant may kill any remaining tumor cells.
Procedure: autologous bone marrow transplantation
Procedure: autologous hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Drug: vincristine sulfate
Radiation: radiation therapy
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma|
- Failure-free survival (FFS) [ Time Frame: At 1 year ] [ Designated as safety issue: No ]FFS experience of each group of patients (distant metastatic CNS positive, distant metastatic CNS negative, and orbit patients) can be adequately modeled using the exponential cure model. We will compare the observed survival experience to the expected distribution using a method adapted from Woolson. The difference between the number of observed and expected failures is approximately normally distributed with independent increments and may be used for interim monitoring using standard group sequential boundaries.
- Response rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]Estimated and a corresponding 95% confidence interval calculated for all strata combined.
- Toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]The toxicity-associated death rate and the percentage of patients for whom an adequate yield of stem cells cannot be harvested will be monitored across all treatment groups collectively. Toxicities will be descriptively summarized.
|Study Start Date:||February 2008|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy, radiation therapy, autologous SCI)
INDUCTION: Vincristine sulfate IV; cisplatin IV; cyclophosphamide IV; and filgrastim (G-CSF) SC on day 3 and continuing until blood counts recover. CONSOLIDATION (stage 4a or 4b disease only): Patients receive carboplatin IV; thiotepa IV; and etoposide IV. AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Autologous hematopoietic stem cell transplantation on day 0 and receive filgrastim (G-CSF) SC beginning on day 1 and continuing until blood counts recover. RADIOTHERAPY: Stage 2 or 3 disease (orbital and/or regional involvement) undergo radiation therapy to initially involved sites beginning within 42 days after the start of course 4 of induction chemotherapy. Stage 4a or 4b disease undergo radiation therapy to sites initially involved based on response beginning approximately 42 days post autologous stem cell infusion. If bone marrow was positive at baseline, bone marrow examinations should be performed after each cycle of chemotherapy prior to stem cell harvesting.
Procedure: autologous bone marrow transplantation
Bone marrow Transplant
Other Names:Procedure: autologous hematopoietic stem cell transplantation
Extraction (apheresis) of haematopoietic stem cellsProcedure: in vitro-treated peripheral blood stem cell transplantation
Peripheral blood stem cell transplantation while in vitro
Other Names:Drug: cisplatin
Other Names:Drug: cyclophosphamide
Other Names:Drug: etoposide
Other Names:Biological: filgrastim
Other Names:Drug: carboplatin
Other Names:Drug: vincristine sulfate
Other Names:Drug: thiotepa
Other Names:Radiation: radiation therapy
I. To estimate the proportion of children with extraocular retinoblastoma who achieve long-term event-free survival after treatment with aggressive multimodality therapy compared to historical controls.
II. To estimate the response rate to the induction phase of the regimen. III. To evaluate the toxicities associated with this regimen.
OUTLINE: This is a multicenter study.
Patients are stratified according to disease stage (stage 2 or 3 [regional extraocular disease] vs stage 4a [disseminated metastatic disease not involving the CNS, including extradural/dural disease without parenchymal or leptomeningeal disease] vs stage 4b [CNS disease, including trilateral retinoblastoma]).
INDUCTION CHEMOTHERAPY: Patients receive vincristine IV on days 0, 7, and 14, cisplatin IV over 6 hours on day 0, cyclophosphamide IV over 1 hour and etoposide IV over 1 hour on days 1 and 2, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 and continuing until blood counts recover.
Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of induction chemotherapy, patients with stage 2 or 3 disease who have at least a partial response proceed to radiotherapy. Patients with stage 4a or 4b disease who have at least a partial response proceed to high-dose consolidation chemotherapy and autologous stem cell infusion.
STEM CELL HARVESTING (stage 4a or 4b disease only): Peripheral blood stem cells (preferred) or bone marrow cells are collected after at least 1 course of induction chemotherapy.
HIGH-DOSE CONSOLIDATION CHEMOTHERAPY (stage 4a or 4b disease only): Patients receive carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3.
AUTOLOGOUS STEM CELL INFUSION (stage 4a or 4b disease only): Patients undergo autologous stem cell infusion on day 0. Patients then receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
RADIOTHERAPY: Patients with stage 2 or 3 disease (orbital and/or regional involvement) undergo radiotherapy to sites that were initially involved beginning within 42 days after the start of course 4 of induction chemotherapy. Patients with stage 4a or 4b disease undergo radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion. Patients with stage 4a disease who achieve a complete response to induction chemotherapy or with less than 5 mm of residual tumor at the time of planned irradiation, or patients with stage 4b disease who achieve a complete response to induction chemotherapy do not undergo radiotherapy.
After completion of study therapy, patients are followed every 3 months for 1 year and then annually thereafter.