Clinical Trials /

Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors

NCT01602666

Description:

This phase II trial studies how well chemotherapy followed by radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors that have not spread to other parts of the brain, spinal canal, or body (localized). Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x rays to kill tumor cells. Giving chemotherapy followed by radiation therapy may kill more tumor cells.

Related Conditions:
  • Central Nervous System Germ Cell Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors
  • Official Title: Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT)

Clinical Trial IDs

  • ORG STUDY ID: ACNS1123
  • SECONDARY ID: NCI-2012-01967
  • SECONDARY ID: CDR0000734032
  • SECONDARY ID: U10CA098543
  • SECONDARY ID: COG-ACNS1123
  • NCT ID: NCT01602666

Conditions

  • Childhood Central Nervous System Germ Cell Tumor
  • Childhood Central Nervous System Germinoma

Interventions

DrugSynonymsArms
carboplatinCarboplat, CBDCA, JM-8, Paraplat, ParaplatinTreatment (combination chemotherapy, radiation therapy)
etoposideEPEG, VP-16, VP-16-213Treatment (combination chemotherapy, radiation therapy)
ifosfamideCyfos, Holoxan, IFF, IFX, IPPTreatment (combination chemotherapy, radiation therapy)

Purpose

Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill tumor cells. Giving chemotherapy with radiation therapy may kill more tumor cells. This phase II trial studies how well chemotherapy and radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns
      of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole
      ventricular-field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy
      craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young
      adults with localized nongerminomatous germ cell tumor (NGGCT) who have a magnetic resonance
      imaging (MRI) and tumor marker criteria (CSF and serum) for confirmed complete response (CR)
      or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid
      (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with
      negative tumor markers who undergo a second-look surgery and are found to have only mature
      teratoma, residual scar or fibrosis, and fit the definition of CR/PR after second-look
      surgery.

      II. To determine, as measured by the 3-year PFS rate and patterns of failure, whether
      simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating
      children and young adults with localized primary central nervous system (CNS) germinoma who
      present with serum and/or CSF human chorionic gonadotropin-beta (hCGβ) =< 50 mIU/mL.

      III. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral
      functioning of children and young adults who are treated with reduced radiation dose and
      volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum
      2 (Germinoma) using the ALTE07C1 protocol (This objective will be assessed independently for
      the two strata).

      SECONDARY OBJECTIVES:

      To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated
      with 30.6 Gy WVI and involved-field radiation therapy (IFR) focal boost to 54 Gy. II. To
      estimate the PFS and OS distributions of localized-germinoma patients who present with serum
      and/or CSF hCGβ ≤ 50 mIU/mL vs serum and/or CSF hCGβ > 50 mIU/mL and =< 100 mIU/mL.

      OUTLINE: This is a multicenter study. Patients are stratified according to localized primary
      disease (nongerminomatous germ cell tumor [NGGCT] vs germinoma).

      Stratum 1 (NGGCT): Patients receive induction therapy comprising carboplatin IV over 15-60
      minutes on day 1 and etoposide IV over 1-2 hours on days 1-3 of courses 1, 3, and 5. Patients
      also receive ifosfamide IV over 1 hour and etoposide over 1-2 hours on days 1-5 of courses 2,
      4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression
      or unacceptable toxicity. Patients with responsive disease (complete [CR] or partial response
      [PR]) to induction chemotherapy undergo radiotherapy once daily (QD) 5 days a week for 6
      weeks. Patients with PR, stable disease (SD), or progressive disease (PD) and normalization
      of tumor levels undergo second-look surgery. Patients who achieve CR or PR after second-look
      surgery undergo radiotherapy.

      Stratum 2 (Germinoma): Patients receive induction therapy comprising carboplatin IV over
      15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every
      21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
      Patients with CR or continued CR undergo radiotherapy QD 5 days a week for approximately 4
      weeks. Patients with PR, SD, or PD with normal tumor markers may undergo second-look surgery.
      Patients found to have mature teratoma or non-viable tumor during surgery undergo
      radiotherapy. Patients with PR or SD with residual disease (=< 1.5 cm) and suprasellar (> 0.5
      cm) or pineal (> 1 cm) involvement and normal tumor markers undergo radiotherapy after
      chemotherapy without second-look surgery.

      After completion of study treatment, patients are followed up every 3 months for 1 year,
      every 4 months for 2 years, and then annually for up to 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (combination chemotherapy, radiation therapy)ExperimentalStratum 1 (NGGCT): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 1 hour and etoposide over 1-2 hours on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive disease (complete [CR] or partial response [PR]) to induction chemotherapy undergo radiotherapy once daily (QD) 5 days a week for 6 weeks. Patients with PR, stable disease (SD), or progressive disease (PD) and normalization of tumor levels undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo radiotherapy. Stratum 2 (Germinoma): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3. Continued (see detailed description)
  • carboplatin
  • etoposide
  • ifosfamide

Eligibility Criteria

        Inclusion and Exclusion Criteria:

          -  Patients must be newly diagnosed with localized primary CNS non germinomatous germ
             cell tumor (NGGCT) (Stratum 1) or localized primary CNS germinoma (Stratum 2); germ
             cell tumors (GCTs) located in the suprasellar, pineal, bifocal (pineal +suprasellar),
             and ventricles are eligible; tumors present in the above mentioned locations and with
             unifocal parenchymal extension are eligible

               -  Stratum 1( NGGCT): Patients must have one of the following criteria:

                    -  Patients with serum and/or CSF hCGβ > 100 mIU/mL or any elevation of serum
                       and CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the institutional
                       normal are eligible, irrespective of biopsy results

                    -  Patients with any of the following elements on biopsy/resection are
                       eligible, irrespective of serum and/or CSF hCGβ and AFP levels: endodermal
                       sinus tumor (yolk sac),embryonal carcinoma, choriocarcinoma,
                       malignant/immature teratoma, and mixed GCT with malignant GCT elements

               -  Stratum 2 (Germinoma): Patients must have one of the following criteria:

                    -  Patients with institutional normal AFP AND hCGβ 5 to ≤ 50 mIU/mL in serum
                       and/or CSF are eligible; no histologic confirmation required

                    -  Patients with bifocal (pineal + suprasellar) involvement or pineal lesion
                       with diabetes insipidus AND hCGβ ≤ 100 mIU/mL and institutional normal AFP
                       in serum and/or CSF are eligible; no histologic confirmation required

                    -  Patients with histologically confirmed germinoma or germinoma mixed with
                       mature teratoma and hCGβ ≤ 100 mIU/mL and institutional normal AFP in serum
                       and/or CSF are eligible

          -  Patients must have negative lumbar CSF cytology; lumbar CSF must be obtained unless
             medically contraindicated

          -  Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123

          -  Patients with mature teratoma with normal tumor markers are not eligible

          -  Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not
             eligible

          -  Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are
             not eligible

          -  Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL

          -  Platelet count ≥ 100,000/μL (transfusion independent)

          -  Hemoglobin ≥ 8.0 g/dL (may receive red blood cell [RBC] transfusions)

          -  Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m² OR 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 to < 2 years of age)

               -  0.8 mg/dL (2 to < 6 years of age)

               -  1.0 mg/dL (6 to < 10 years of age)

               -  1.2 mg/dL (10 to < 13 years of age)

               -  1.5 mg/dL (male) and 1.4 mg/dL (female) (13 to < 16 years of age)

               -  1.7 mg/dL (male) and 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 glutamic pyruvate transaminase(SGPT) (alanine aminotransferase [ALT]) < 2.5
             times ULN

          -  Patients with seizure disorder may be enrolled if well controlled

          -  Patients must not be in status, coma, or assisted ventilation prior to study
             enrollment

          -  Female patients who are pregnant are ineligible

          -  Lactating females are not eligible unless they have agreed not to breastfeed their
             infants

          -  Female patients of childbearing potential are not eligible unless a negative pregnancy
             test result has been obtained

          -  Sexually active patients of reproductive potential are not eligible unless they have
             agreed to use an effective contraceptive method for the duration of their study
             participation

          -  Patients who had more than 1 prior surgery/biopsy are eligible

          -  Patients must not have received any prior tumor-directed therapy other than surgical
             intervention and corticosteroids.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:3 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:3-year PFS rate with NGGCT
Time Frame:Three years follow-up after last patient enrollment
Safety Issue:
Description:Kaplan-Meier estimates will be provided.

Secondary Outcome Measures

Measure:Estimation of the PFS distribution of patients with NGGCT treated with IFR
Time Frame:Up to 5 years
Safety Issue:
Description:Kaplan-Meier estimates will be provided.
Measure:Estimation of the OS distribution of patients with NGGCT treated with IFR assessed
Time Frame:Up to 5 years
Safety Issue:
Description:Kaplan-Meier estimates will be provided.
Measure:Estimation of the PFS distribution of patients with localized germinoma patients and CSF serum hCGβ of 50 mIU/mL or less or CSF serum hCGβ greater than 50 mIU/mL and less than or equal to 100 mIU/mL
Time Frame:Up to 5 years
Safety Issue:
Description:Kaplan-Meier estimates will be provided.
Measure:Estimation of the OS distribution of patients with localized germinoma patients and CSF serum hCGβ of 50 mIU/mL or less or CSF serum hCGβ greater than 50 mIU/mL and less than or equal to 100 mIU/mL
Time Frame:Up to 5 years
Safety Issue:
Description:Kaplan-Meier estimates will be provided.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Children's Oncology Group

Last Updated

January 22, 2018