Skip to content
Triangle logo TriangleGet started
← Study library

NCT00047320 · CITED IN SOURCE DOCUMENTS

Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors

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

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2018-02-14

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it is no longer present by conventional imaging and tumor markers from serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill more tumor cells. PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without surgery and with or without high dose chemotherapy and peripheral stem cell transplantation, can increase response rates prior to radiation therapy and increase progression free and overall surviving patients with newly diagnosed intracranial germ cell tumors.

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

Response to Induction Chemotherapy

→

outcome · POSTED

The Probability of Event-free Survival (EFS)

→

outcome · POSTED

Progression-free Survival (PFS)

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Number of Patients Experiencing Toxic Death

→

outcome · POSTED

Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
DISEASE CHARACTERISTICS: * One of the following diagnoses: * Histologically confirmed intracranial non-germinomatous germ cell tumor (NGGCT) of 1 of the following types: * Endodermal sinus tumor (yolk sac tumor) * Embryonal carcinoma * Choriocarcinoma * Immature teratoma and teratoma with malignant transformation * Mixed germ cell tumor * Histologically confirmed germinoma with elevation of serum/CSF beta human chorionic gonadotropin (HCG) levels greater than 50 mIU/mL or any serum/CSF alpha-fetoprotein (AFP) levels greater than 10 ng/ml or above institutional norm * Histologically unconfirmed pineal and/or suprasellar tumors with serum/CSF beta HCG levels greater than 50 mIU/mL or AFP levels greater than 10 ng/ml or above institutional norm * Patients with normal AFP and beta HCG \< 50 mIU/mL without histologic diagnosis of a NGGCT or patients with pure germinoma without elevation of tumor marker are ineligible * Initial diagnosis within the past 31 days PATIENT CHARACTERISTICS: Age * 3 to 24 at diagnosis Performance status * No minimum performance level Life expectancy * At least 8 weeks Hematopoietic * Absolute neutrophil count at least 1,000/mm\^3 * Platelet count at least 100,000/mm\^3 (transfusion independent) * Hemoglobin at least 10.0 g/dL (transfusion allowed) Hepatic * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * ALT no greater than 2.5 times ULN Renal * Creatinine no greater than 1.5 times ULN OR * Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min Pulmonary * No assisted ventilation Other * Seizure disorders allowed * No patients in status or coma * Not pregnant or nursing * Negative pregnancy test * Fertile patient must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * Prior corticosteroids allowed * Concurrent corticosteroids allowed * Concurrent endocrine replacement therapy allowed (e.g., L-thyroxine, testosterone, estrogen, desmopressin acetate) * No concurrent growth hormone therapy Radiotherapy * Not specified Surgery * More than 1 prior surgery allowed Other * No other prior therapy for malignancy
healthy Volunteers
false
maximum Age
24 Years
minimum Age
3 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC \> 750/L and platelets \> 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
    intervention Names
    1. Drug: carboplatin
    2. Drug: etoposide
    3. Drug: ifosfamide
    4. Drug: thiotepa
    5. Procedure: adjuvant therapy
    6. Procedure: conventional surgery
    7. Procedure: neoadjuvant therapy
    8. Procedure: peripheral blood stem cell transplantation
    9. Radiation: radiation therapy
    label
    Radiation Therapy (CR from Induction)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    description
    Given IV
    name
    carboplatin
    other Names
    1. Paraplatin
    2. NSC #241240
    type
    DRUG
  2. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    description
    Given IV
    name
    etoposide
    other Names
    1. VP-16
    2. VePesid
    3. Etopophos
    4. NSC #141540
    type
    DRUG
  3. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    description
    Given IV
    name
    ifosfamide
    other Names
    1. Isophosphamide
    2. Iphosphamide
    3. Z4942
    4. Ifex
    5. NSC #109724
    type
    DRUG
  4. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    description
    Given IV
    name
    thiotepa
    other Names
    1. Tespa
    2. Thiophosphamide
    3. Triethylenethiophosphoramide Tspa
    4. WR-45312
    5. NSC #6396
    type
    DRUG
  5. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    name
    adjuvant therapy
    type
    PROCEDURE
  6. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    name
    conventional surgery
    type
    PROCEDURE
  7. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    name
    neoadjuvant therapy
    type
    PROCEDURE
  8. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    name
    peripheral blood stem cell transplantation
    type
    PROCEDURE
  9. arm Group Labels
    1. Radiation Therapy (CR from Induction)
    description
    craniospinal irradiation
    name
    radiation therapy
    other Names
    1. Craniospinal irradiation (CSI) followed by boost radiation to the sites of gross disease at diagnosis.
    type
    RADIATION
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
104
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response.
    measure
    Response to Induction Chemotherapy
    time Frame
    18 weeks
secondary Outcomes
  1. description
    Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. Event-free survival was estimated by KM estimate.
    measure
    The Probability of Event-free Survival (EFS)
    time Frame
    At 3 years from study entry
  2. description
    Progression-free Survival was defined as time from study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis. Progression -free survival was estimated by KM estimate.
    measure
    Progression-free Survival (PFS)
    time Frame
    At 3 years from study entry
  3. description
    Overall Survival was defined as time from study entry to death from any cause. Overall survival was estimated by KM estimate.
    measure
    Overall Survival (OS)
    time Frame
    At 3 years from study entry
  4. description
    Toxic death, defined as death predominantly attributable to treatment-related causes.
    measure
    Number of Patients Experiencing Toxic Death
    time Frame
    During chemotherapy (up to 18 weeks)
  5. description
    The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy.
    measure
    Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity
    time Frame
    During chemotherapy(up to 18 weeks)
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it is no longer present by conventional imaging and tumor markers from serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill more tumor cells. PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without surgery and with or without high dose chemotherapy and peripheral stem cell transplantation, can increase response rates prior to radiation therapy and increase progression free and overall surviving patients with newly diagnosed intracranial germ cell tumors.
detailed Description
OBJECTIVES: * Determine the response rate of patients with non-germinomatous germ cell tumors treated with neoadjuvant chemotherapy. * Determine the progression-free survival and overall survival of patients treated with neoadjuvant chemotherapy with or without second-look surgery followed by radiotherapy with or without autologous peripheral blood stem cell transplantation (PBSCT). * Determine whether additional complete responses can be achieved after high-dose thiotepa and etoposide with PBSCT in patients with persistently positive markers, histological evidence of residual malignant elements, or unresectable residual tumors after initial neoadjuvant chemotherapy. * Determine patterns of recurrence in patients treated with this regimen. * Correlate tumor marker response with radiographic and clinical measures of response, as well as findings at second-look surgery in patients with radiological evidence of residual disease. OUTLINE: * Induction chemotherapy: * Courses 1, 3, and 5: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3. Beginning on day 4, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) for 10 days or until blood counts recover. Courses are 3 weeks in duration. * Courses 2, 4, and 6: Patients receive etoposide IV over 1 hour followed by ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive G-CSF IV or SC for 10 days or until blood counts recover. Courses are 3 weeks in duration. Patients undergo re-evaluation. Patients with a complete response (CR) go directly to radiotherapy. Approximately 3 weeks after completion of induction chemotherapy, all patients with less than a CR are encouraged to undergo second-look surgery. After second-look surgery, patients with a CR or a partial response (PR) go directly to radiotherapy. Patients with less than a PR undergo consolidation chemotherapy with peripheral blood stem cell rescue (PBSC) followed by radiotherapy. * Consolidation chemotherapy: Patients undergo PBSC collection. Patients receive G-CSF SC until PBSC collection is complete. Patients then receive thiotepa IV over 3 hours followed by etoposide IV over 3 hours on days -5 to -3. PBSCs are reinfused on day 0. Beginning on day 1 and continuing until blood counts recover, patients receive G-CSF SC daily. * Radiotherapy: All patients receive radiotherapy once daily 5 days a week for 5-6 weeks beginning after recovery from induction chemotherapy or second-look surgery or within 9 weeks after PBSC reinfusion. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 80-100 patients will be accrued for this study within 36-42 months.
Source references
references
  1. citation
    Fangusaro J, Wu S, MacDonald S, Murphy E, Shaw D, Bartels U, Khatua S, Souweidane M, Lu HM, Morris D, Panigrahy A, Onar-Thomas A, Fouladi M, Gajjar A, Dhall G. Phase II Trial of Response-Based Radiation Therapy for Patients With Localized CNS Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study. J Clin Oncol. 2019 Dec 1;37(34):3283-3290. doi: 10.1200/JCO.19.00701. Epub 2019 Sep 23.
    pmid
    31545689
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-50c37c63e3e744b6c123
      requested nct id
      NCT00047320
      primary nct id
      NCT00047320
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      8702bd0cf75b16cfc52d3d29d6c453de330d2cbe8d7e5f3180a4cccb3dec27f3
      payload sha256
      8ab189ad706e38c56bbcd3d14823febb51526ec4daa23e8ed235cc3c776089e1
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-50c37c63e3e744b6c123
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT00047320
      occurrences
      1. context exact
        py followed by radiation therapy):</p> <div class="pdq-content-list"><ol id="_1814"><li>A Children's Oncology Group (COG) study (<a href="/clinicaltrials/NCT00047320">ACNS0122 [NCT00047320]</a>) evaluated neoadjuvant chemotherapy followed by radiation therapy for children with localized NGGCTs.[<a href="#cit/section_5.2">2<
        end
        96391
        exact text
        NCT00047320
        start
        96380
      2. context exact
        n therapy):</p> <div class="pdq-content-list"><ol id="_1814"><li>A Children's Oncology Group (COG) study (<a href="/clinicaltrials/NCT00047320">ACNS0122 [NCT00047320]</a>) evaluated neoadjuvant chemotherapy followed by radiation therapy for children with localized NGGCTs.[<a href="#cit/section_5.2">2</a>] Neoadjuvant chemot
        end
        96414
        exact text
        NCT00047320
        start
        96403
      3. context exact
        trial, causing early stoppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the <a href="/clinicaltrials/NCT00047320">ACNS0122 (NCT00047320)</a> trial.<p id="_1870" tabindex="-1"> Patients in this study received six cycles of chemotherapy with carboplatin and etoposide altern
        end
        98576
        exact text
        NCT00047320
        start
        98565
      4. context exact
        toppage of the protocol. This is compared with 8% of patients who developed a similar pattern of relapse in the <a href="/clinicaltrials/NCT00047320">ACNS0122 (NCT00047320)</a> trial.<p id="_1870" tabindex="-1"> Patients in this study received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide a
        end
        98599
        exact text
        NCT00047320
        start
        98588
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/4e7a33a8cfb84ff4e4.html
      source file sha256
      8702bd0cf75b16cfc52d3d29d6c453de330d2cbe8d7e5f3180a4cccb3dec27f3
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:32.688337+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      8320ccfb31415815eab14c8336092aa4b9bb6a5abe4c47bef9b6fec1cb75f8eb
      source title
      Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: October 8, 2024
        datetime
        2024-10-08T12:00:00Z
        display
        October 8, 2024

    Preserved source evidence · Not medical advice