Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00554788
First received: November 6, 2007
Last updated: March 21, 2014
Last verified: March 2014
  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. 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.


Condition Intervention Phase
Extraocular Retinoblastoma
Procedure: autologous bone marrow transplantation
Procedure: autologous hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Drug: cisplatin
Drug: cyclophosphamide
Drug: etoposide
Biological: filgrastim
Drug: carboplatin
Drug: vincristine sulfate
Drug: thiotepa
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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. The observed survival experience will be compared 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.


Secondary Outcome Measures:
  • Response rate to the induction phase of the regimen using a modified version of the international criteria for neuroblastoma response [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated and a corresponding 95% confidence interval calculated for all strata combined.

  • Incidence of adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ 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.


Estimated Enrollment: 60
Study Start Date: February 2008
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, radiotherapy, autologous SCI)

INDUCTION: Patients receive vincristine sulfate IV; cisplatin IV; cyclophosphamide IV; and G-CSF (filgrastim) SC beginning 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): Patients undergo autologous hematopoietic stem cell transplantation on day 0 and 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 radiation therapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.

Procedure: autologous bone marrow transplantation
Undergo peripheral blood stem cell or bone marrow transplant
Other Names:
  • ABMT
  • bone marrow transplantation, autologous
  • transplantation, autologous bone marrow
Procedure: autologous hematopoietic stem cell transplantation
Undergo peripheral blood stem cell or bone marrow transplant
Procedure: in vitro-treated peripheral blood stem cell transplantation
Undergo peripheral blood stem cell or bone marrow transplant
Other Names:
  • in vitro-treated PBPC transplantation
  • in vitro-treated PBSC
  • in vitro-treated peripheral blood progenitor cell transplantation
  • PBPC transplantation, in vitro-treated
  • peripheral blood progenitor cell transplantation, in vitro-treated
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: thiotepa
Given IV
Other Names:
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

Detailed Description:

OBJECTIVES:

I. To estimate the proportion of 3 groups of patients with extraocular retinoblastoma (stage 2 and 3: regional extra-ocular disease;, stage 4a: disseminated metastatic disease not involving the central nervous system [CNS]; or stage 4b: patients with CNS disease) 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:

INDUCTION CHEMOTHERAPY: Patients receive vincristine intravenously (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 filgrastim subcutaneously (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 for 9 years.

  Eligibility

Ages Eligible for Study:   up to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologic or cytologic verification of extra-ocular retinoblastoma; extra-ocular disease includes orbital disease, optic nerve involvement at the surgical margin, regional nodal disease, and/or overt distant metastatic disease (at sites such as bone, bone marrow, liver and/or the central nervous system); patients with trilateral retinoblastoma will also be included in this protocol

    • Patients with a CNS lesion consistent with trilateral or stage 4b disease may be enrolled without tissue confirmation if (1) unequivocal leptomeningeal disease is present on brain or spine magnetic resonance imaging (MRI) scan and/or (2) the primary tumor is at least 2 cm in diameter, predominantly solid, and demonstrates enhancement on the post-gadolinium images; however, even in such cases surgery should be given serious consideration
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • No prior chemotherapy or radiotherapy for the extra-ocular retinoblastoma may have been administered prior to entering this study; prior treatment (chemotherapy and/or radiation therapy) for intra-ocular retinoblastoma is permissible
  • Peripheral absolute neutrophil count (ANC) >= 750/uL

    • If the ANC and/or platelet count are not adequate, but due to bone marrow metastatic disease, these criteria will be waived
  • Platelet count >= 75,000/uL (transfusion independent)

    • If the ANC and/or platelet count are not adequate, but due to bone marrow metastatic disease, these criteria will be waived
  • 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)
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN)
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) for human studies must be met
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00554788

  Show 65 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Ira Dunkel, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00554788     History of Changes
Other Study ID Numbers: ARET0321, NCI-2009-00421, COG-ARET0321, CDR0000573987, ARET0321, ARET0321, U10CA098543
Study First Received: November 6, 2007
Last Updated: March 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Eye Neoplasms
Eye Diseases
Retinal Diseases
Retinoblastoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Neoplasms by Site
Etoposide phosphate
Cisplatin
Cyclophosphamide
Etoposide
Thiotepa
Vincristine
Carboplatin
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on August 21, 2014