Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma
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Purpose
RATIONALE: 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.
PURPOSE: 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..
| Condition | Intervention | Phase |
|---|---|---|
|
Retinoblastoma |
Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Drug: thiotepa Drug: vincristine sulfate Procedure: autologous bone marrow transplantation Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Primary Purpose: Treatment |
| Official Title: | A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma |
- Event-free survival [ Designated as safety issue: No ]
- Response rate [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 60 |
| Study Start Date: | February 2008 |
| Estimated Primary Completion Date: | February 2017 (Final data collection date for primary outcome measure) |
OBJECTIVES:
- 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.
- To estimate the response rate to the induction phase of the regimen.
- 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.
Eligibility| Ages Eligible for Study: | up to 10 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed extraocular retinoblastoma, meeting 1 of the following criteria:
- Stage 2 or 3 disease (regional extraocular disease)
- Stage 4a disease (disseminated metastatic disease not involving the CNS, including extradural/dural disease without parenchymal or leptomeningeal disease)
Stage 4b disease or CNS lesion consistent with trilateral retinoblastoma allowed provided the following:
- Unequivocal leptomeningeal disease is present on brain or spine by MRI scan
- Primary tumor is ≥ 2 cm in diameter, predominantly solid, and demonstrates enhancement on the post-Gadolinium images
Extraocular disease includes any of the following:
- Orbital disease
- Optic nerve involvement at the surgical margin
- Regional nodal disease
- Overt distant metastatic disease (at sites such as bone, bone marrow, liver, and/or the CNS)
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2
- ANC ≥ 750/μL*
- Platelet count ≥ 75,000/μL* (transfusion independent)
Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 month to < 6 months of age)
- 0.5 mg/dL (6 months to < 1 year of age)
- 0.6 mg/dL (1 years to < 2 years of age)
- 0.8 mg/dL (2 years to < 6 years of age)
- 1.0 mg/dL (6 years to < 10 years of age)
- 1.2 mg/dL (10 years to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN NOTE: *Inadequate ANC and/or platelet count due to bone marrow metastatic disease allowed
PRIOR CONCURRENT THERAPY:
No prior chemotherapy or radiotherapy for extraocular retinoblastoma
- Prior chemotherapy and/or radiation therapy for intraocular retinoblastoma allowed
No other concurrent anticancer chemotherapy, radiotherapy, or immunomodulating agents (including steroids)
- Corticosteroid therapy is allowed only for treatment of increased intracranial pressure in patients with CNS tumors
- Dexamethasone should not be prescribed as an anti-emetic
Contacts and Locations
Show 58 Study Locations| Study Chair: | Ira Dunkel, MD | Memorial Sloan-Kettering Cancer Center |
| Investigator: | Eric F. Grabowski, MD, ScD | Massachusetts General Hospital |
More Information
Additional Information:
No publications provided
| Responsible Party: | Gregory H. Reaman, Children's Oncology Group - Group Chair Office |
| ClinicalTrials.gov Identifier: | NCT00554788 History of Changes |
| Other Study ID Numbers: | CDR0000573987, COG-ARET0321 |
| Study First Received: | November 6, 2007 |
| Last Updated: | November 3, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
extraocular retinoblastoma |
Additional relevant MeSH terms:
|
Retinoblastoma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Retinal Neoplasms Eye Neoplasms Neoplasms by Site Eye Diseases Retinal Diseases Cisplatin Cyclophosphamide |
Etoposide Thiotepa Vincristine Carboplatin Lenograstim Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents |
ClinicalTrials.gov processed this record on May 23, 2013