Skip to content
Triangle logo TriangleGet started
← Study library

NCT00554788 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2025-01-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Event-free Survival (EFS)

→

outcome · POSTED

Response Rate to the Induction Phase of the Regimen

→

outcome · POSTED

Percentage of Participants With Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility 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
healthy Volunteers
false
maximum Age
10 Years
sex
ALL
std Ages
  1. CHILD
Treatment arms and interventions
arm Groups
  1. description
    INDUCTION: Patients receive vincristine IV; cisplatin IV; cyclophosphamide IV; and G-CSF 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 stem cell infusion 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 radiotherapy to sites initially involved based on response beginning approximately 42 days after autologous stem cell infusion.
    intervention Names
    1. Procedure: Autologous Bone Marrow Transplantation
    2. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    3. Drug: Carboplatin
    4. Drug: Cisplatin
    5. Drug: Cyclophosphamide
    6. Drug: Etoposide
    7. Biological: Filgrastim
    8. Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation
    9. Radiation: Radiation Therapy
    10. Drug: Thiotepa
    11. Drug: Vincristine Sulfate
    label
    Treatment (chemotherapy, radiotherapy, autologous SCI)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Undergo peripheral blood stem cell or bone marrow transplant
    name
    Autologous Bone Marrow Transplantation
    other Names
    1. ABMT
    2. Autologous Blood and Marrow Transplantation
    3. Autologous Bone Marrow Transplant
    4. Autologous Marrow Transplantation
    type
    PROCEDURE
  2. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Undergo peripheral blood stem cell or bone marrow transplant
    name
    Autologous Hematopoietic Stem Cell Transplantation
    other Names
    1. AHSCT
    2. Autologous
    3. Autologous Hematopoietic Cell Transplantation
    4. Autologous Stem Cell Transplant
    5. Autologous Stem Cell Transplantation
    6. Stem Cell Transplantation, Autologous
    type
    PROCEDURE
  3. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Given IV
    name
    Carboplatin
    other Names
    1. Blastocarb
    2. Carboplat
    3. Carboplatin Hexal
    4. Carboplatino
    5. Carboplatinum
    6. Carbosin
    7. Carbosol
    8. Carbotec
    9. CBDCA
    10. Displata
    11. Ercar
    12. JM-8
    type
    DRUG
  4. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Given IV
    name
    Cisplatin
    other Names
    1. Abiplatin
    2. Blastolem
    3. Briplatin
    4. CDDP
    5. Cis-diammine-dichloroplatinum
    6. Cis-diamminedichloridoplatinum
    7. Cis-diamminedichloro Platinum (II)
    8. Cis-diamminedichloroplatinum
    9. Cis-dichloroammine Platinum (II)
    10. Cis-platinous Diamine Dichloride
    11. Cis-platinum
    12. Cis-platinum II
    type
    DRUG
  5. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Given IV
    name
    Cyclophosphamide
    other Names
    1. (-)-Cyclophosphamide
    2. 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    3. Asta B 518
    4. B 518
    5. B-518
    6. B518
    7. Carloxan
    8. Ciclofosfamida
    9. Ciclofosfamide
    10. Cicloxal
    11. Clafen
    12. Claphene
    type
    DRUG
  6. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Given IV
    name
    Etoposide
    other Names
    1. Demethyl Epipodophyllotoxin Ethylidine Glucoside
    2. EPEG
    3. Lastet
    4. Toposar
    5. Vepesid
    6. VP 16
    7. VP 16-213
    8. VP 16213
    9. VP-16
    10. VP-16-213
    11. VP-16213
    12. VP16
    type
    DRUG
  7. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Given SC
    name
    Filgrastim
    other Names
    1. Filgrastim Biosimilar Filgrastim-sndz
    2. Filgrastim Biosimilar Tbo-filgrastim
    3. Filgrastim XM02
    4. Filgrastim-aafi
    5. Filgrastim-ayow
    6. Filgrastim-sndz
    7. G-CSF
    8. Granix
    9. Neupogen
    10. Neutroval
    11. Nivestim
    12. Nivestym
    type
    BIOLOGICAL
  8. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Undergo peripheral blood stem cell or bone marrow transplant
    name
    In Vitro-Treated Peripheral Blood Stem Cell Transplantation
    other Names
    1. in vitro-treated PBPC transplantation
    2. in vitro-treated peripheral blood progenitor cell transplantation
    type
    PROCEDURE
  9. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Undergo radiotherapy
    name
    Radiation Therapy
    other Names
    1. Cancer Radiotherapy
    2. Energy Type
    3. ENERGY_TYPE
    4. Irradiate
    5. Irradiated
    6. Irradiation
    7. Radiation
    8. Radiation Therapy, NOS
    9. Radiotherapeutics
    10. Radiotherapy
    11. RT
    12. Therapy, Radiation
    type
    RADIATION
  10. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Given IV
    name
    Thiotepa
    other Names
    1. 1,1',1''-Phosphinothioylidynetrisaziridine
    2. Girostan
    3. N,N', N''-Triethylenethiophosphoramide
    4. Oncotiotepa
    5. SH 105
    6. SH-105
    7. SH105
    8. STEPA
    9. Tepadina
    10. Tepylute
    11. TESPA
    12. Tespamin
    type
    DRUG
  11. arm Group Labels
    1. Treatment (chemotherapy, radiotherapy, autologous SCI)
    description
    Given IV
    name
    Vincristine Sulfate
    other Names
    1. Kyocristine
    2. Leurocristine Sulfate
    3. Leurocristine, sulfate
    4. Oncovin
    5. Vincasar
    6. Vincosid
    7. Vincrex
    8. Vincristine, sulfate
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
60
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    The probability of surviving patients who did not experience events at 1 year following enrollment. An event is defined as relapse, second malignancy, or death from any cause.
    measure
    Event-free Survival (EFS)
    time Frame
    At 1 year
secondary Outcomes
  1. description
    This study used a modified version of the international criteria for neuroblastoma response. The response rate to the induction phase of the regimen and a corresponding 95% confidence interval will be calculated for all strata combined.
    measure
    Response Rate to the Induction Phase of the Regimen
    time Frame
    12 weeks after participant received the first dose
  2. description
    Grade 3 and higher toxicities will be descriptively summarized.
    measure
    Percentage of Participants With 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
Full study description
brief Summary
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.
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.
Source references
references
  1. citation
    Dunkel IJ, Piao J, Chantada GL, Banerjee A, Abouelnaga S, Buchsbaum JC, Merchant TE, Granger MM, Jubran RF, Weinstein JL, Saguilig L, Abramson DH, Krailo MD, Rodriguez-Galindo C, Chintagumpala MM. Intensive Multimodality Therapy for Extraocular Retinoblastoma: A Children's Oncology Group Trial (ARET0321). J Clin Oncol. 2022 Nov 20;40(33):3839-3847. doi: 10.1200/JCO.21.02337. Epub 2022 Jul 12.
    pmid
    35820112
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-68555b0da627c1f67d94
      requested nct id
      NCT00554788
      primary nct id
      NCT00554788
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      c4e87fa131e6c3c15c159ccd775bc9d879890fe6a95e4023b14c1a2d9ed6cd52
      payload sha256
      becac1a08e8333812cf9be582566b00f0d094b3fc153a6a2c5893cbb18a1d9b0
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-68555b0da627c1f67d94
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT00554788
      occurrences
      1. context exact
        are used.</p> <p id="_2820" tabindex="-1">The Children&#8217;s Oncology Group (COG) performed a prospective international trial (<a href="/clinicaltrials/NCT00554788">ARET0321 [NCT00554788]</a>) that included patients with extraocular retinoblastoma. The study showed that intensified therapy improved the outcomes of patient
        end
        222062
        exact text
        NCT00554788
        start
        222051
      2. context exact
        id="_2820" tabindex="-1">The Children&#8217;s Oncology Group (COG) performed a prospective international trial (<a href="/clinicaltrials/NCT00554788">ARET0321 [NCT00554788]</a>) that included patients with extraocular retinoblastoma. The study showed that intensified therapy improved the outcomes of patients with stage II, III or
        end
        222085
        exact text
        NCT00554788
        start
        222074
      3. context exact
        of measurable disease.[<a href="#cit/section_7.1">1</a>] </p> <p id="_2822" tabindex="-1">The COG conducted a prospective study (<a href="/clinicaltrials/NCT00554788">ARET0321 [NCT00554788]</a>) of patients with extraocular retinoblastoma, which included patients with stage IVb disease who were treated with four cycles of i
        end
        226584
        exact text
        NCT00554788
        start
        226573
      4. context exact
        <a href="#cit/section_7.1">1</a>] </p> <p id="_2822" tabindex="-1">The COG conducted a prospective study (<a href="/clinicaltrials/NCT00554788">ARET0321 [NCT00554788]</a>) of patients with extraocular retinoblastoma, which included patients with stage IVb disease who were treated with four cycles of induction therapy (vincr
        end
        226607
        exact text
        NCT00554788
        start
        226596
      5. context exact
        etastases may develop in the bones, bone marrow, and, less frequently, the liver. The COG conducted a prospective international trial (<a href="/clinicaltrials/NCT00554788">ARET0321 [NCT00554788]</a>) for patients with extraocular retinoblastoma. The study showed that intensified therapy improved the outcomes of patients with sta
        end
        230238
        exact text
        NCT00554788
        start
        230227
      6. context exact
        n the bones, bone marrow, and, less frequently, the liver. The COG conducted a prospective international trial (<a href="/clinicaltrials/NCT00554788">ARET0321 [NCT00554788]</a>) for patients with extraocular retinoblastoma. The study showed that intensified therapy improved the outcomes of patients with stage IVa disease.[<a href
        end
        230261
        exact text
        NCT00554788
        start
        230250
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/53a34c879ce741bb37.html
      source file sha256
      c4e87fa131e6c3c15c159ccd775bc9d879890fe6a95e4023b14c1a2d9ed6cd52
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:22:14.810107+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      1b536ad649b86efa7e73bc175386a3008db235881e993ea7084ddedd7ac4edba
      source title
      Retinoblastoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 3, 2025
        datetime
        2025-04-03T12:00:00Z
        display
        April 3, 2025

    Preserved source evidence · Not medical advice