A Phase 2 Trial of Chemotherapy followed by Response-Based Whole Ventricular & Spinal Canal Irradiation (WVSCI) for Patients with Localized Non-Germinomatous Central Nervous System Germ Cell Tumor.

S
Sandeep Batra, MD

Primary Investigator

Enrolling By Invitation
3 years - 30 years
All
Phase 2
160 participants needed
1 Location

Brief description of study

What is the purpose of this study?
This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients withgerminomatous germ cell tumors (NGGCT) that have not spread to other parts of the brainbody (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dosehemotherapy followed by conventional RT in patients who did not respond to inductionhemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, byg them from dividing, or by stopping them from spreading. Radiation therapy uses highgy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies havehown that patients with newly-diagnosed localized NGGCT, whose disease responds well tohemotherapy before receiving radiation therapy, are more likely to be free of the diseaseger time than are patients for whom the chemotherapy does not efficiently eliminateduce the size of the tumor. The purpose of this study is to see how well the tumorsd to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dosehemotherapy and a stem cell transplant before RT to the whole brain and spine. Givingbased on the response to induction chemotherapy may lower the side effects ofdiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the study?

INDUCTION CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of cycles 1, 3, and 5. Patients alsove ifosfamide IV over 60 minutes and etoposide IV over 60-120 minutes on days 1-5 ofycles 2, 4, and 6. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients are assigned to 1 of 2 plans (ventricular + spinal canal irradiation [WVSCI] or high-dose chemotherapy with peripheral stem cell rescue [HDCSCR]) based on response toduction chemotherapy:
  • Patients who achieve radiographic CR/PR with marker normalization proceed to WVSCI. Patients who achieve radiographic CR without marker normalization proceed to HDCSCR.
  • Patients who achieve less than radiographic CR/PR with marker normalization proceed tod-look surgery (unless contraindicated). If second-look surgery reveals matureviable tumor, proceed to WVSCI. If second-look surgery reveals viableumor, proceed to HDCSCR. Patients who are unable to undergo second-look surgery areved from protocol therapy but remain on study for follow-up.
  • Patients who achieve less than radiographic CR/PR without marker normalization proceedd-look surgery (unless contraindicated). Patients then proceed to HDCSCRgardless of whether or not a second-look surgery is performed.
  • Patients who achieve radiographic PR without marker normalization proceed to second-lookurgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whetherd-look surgery is performed.
PLAN A (WVSCI THERAPY): Within 6 weeks of the end of induction chemotherapy or second-lookurgery, patients undergo WVSCI once daily (QD) for 5 days weekly (17 fractions followed by a boost dose for 13 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.
PLAN B (CONSOLIDATION THERAPY [HDCSCR]): Within 6-8 weeks of the end of inductionhemotherapy or second-look surgery, patients receive etoposide IV and thiotepa IV over 3 hours on days -5 to -3 and undergo peripheral blood stem cell (PBSC) transplant on day 0. Patients then undergo radiation therapy QD for 5 days weekly (20 fractions followed by a boost dose for 10 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 10 years.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Riley, Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma, Embryonal Carcinoma, Immature Teratoma, Malignant Teratoma, Mixed Germ Cell Tumor, Pineal Region Germ Cell Tumor, Pineal Region Immature Teratoma, Pineal Region Yolk Sac Tumor, Suprasellar Germ Cell Tumor
  • Age: 3 years - 30 years
  • Gender: All

Inclusion Criteria:
  • Patients must be >= 3 years and < 30 years at the time of study enrollment
  • Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellard/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevationAFP above institutional normal or > 10 ng/mL or human chorionic gonadotropin (hCG)beta > 100 mIU/mL. Suprasellar, pineal and bifocal tumors are included. (CSF tumorkers and cytology must be within 21 days prior to enrollment and within 35 daysherapy [repeat if necessary]. Serum tumor markers, AFP andhCGbeta must be within 7 days prior to enrollment and start of protocol therapy[repeat if necessary]). Basal ganglia or other primary sites are excluded
  • Patients with any of the following pathological elements are eligible: endodermalus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratomad mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignantd above are present. Patients with only mature teratoma are excluded.Patients with pure germinoma admixed with mature teratoma are excluded (would begible for pure germinoma protocols)
  • Patients must have a cranial magnetic resonance imaging (MRI) with and withoutgadolinium at diagnosis/prior to enrollment. If surgical resection is performed,ust have pre-operative and post operative brain MRI with and withoutgadolinium. The post operative brain MRI should be obtained within 72 hours ofurgery. If patient has a biopsy only, post-operative brain MRI is recommended but notquired (within 14 days prior to study enrollment)
  • Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to. Spine MRI with and without gadolinium is recommended (within 14 days priorudy enrollment)
  • Lumbar CSF must be obtained prior to study enrollment unless medicallydicated. If a patient undergoes surgery and lumbar CSF cytology cannot bebtained at the time of surgery, then it should be performed at least 10 dayswing surgery and prior to study enrollment. False positive cytology can occurwithin 10 days of surgery
  • Patients must have CSF tumor markers obtained prior to enrollment unless medicallydicated. Ventricular CSF obtained at the time of CSF diversion procedure (ifd) is acceptable for tumor markers but lumbar CSF is preferred. In case CSFdiversion and biopsy/surgery are combined, CSF tumor markers should be collected first
  • Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to)
  • Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to)
  • Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70L/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days):
    • Age: Maximum serum creatinine (mg/dL)
      • 3 to < 6 years: 0.8 (male), 0.8 (female)
      • 6 to < 10 years: 1 (male), 1 (female)
      • 10 to < 13 years: 1.2 (male), 1.2 (female)
      • 13 to < 16 years: 1.5 (male), 1.4 (female)
      • >= 16 years: male (1.7), 1.4 (female)

  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to

    enrollment)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135/L (within 7 days prior to enrollment)
    • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to thevalue of 45 U/L
  • Central nervous system function defined as:
    • Patients with seizure disorder may be enrolled if on anticonvulsants and welld
    • Patients must not be in status epilepticus, coma or assisted ventilation prior toudy enrollment

  • Protocol therapy must begin within 31 calendar days of definitive surgery or clinical

    diagnosis. If a biopsy only was performed, the biopsy date will be considered the datedefinitive surgery. For patients who have a biopsy or incomplete resection atdiagnosis followed by additional surgery, the date of the last resection will bedered the date of definitive surgery.
  • All patients and/or their parents or legal guardians must sign a written informed
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute(NCI) requirements for human studies must be met
  • NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT:
  • English-, Spanish-, or French- speaking
    • Note: Patients who speak a language other than English, Spanish, or French willbe allowed to participate in ACNS2021 but will not complete the neurocognitived quality of life assessments

  • No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g.,

    Down syndrome, fragile X, William syndrome, intellectual disability). Patients withF1 will be allowed to participate
  • Additional eligibility criteria for the COG Standardized Neuropsychological Batteryy: must be at a site that has a psychologist to administer the battery
    • Note: If not eligible for the COG Standardized Battery, patients should stillhe Behavior Rating Inventory of Executive Function, Second Edition(BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive BehaviorAssessment System Third Edition (ABAS-3), and Behavior Assessment System forChildren, Third Edition (BASC-3) questionnaires
Exclusion Criteria:
  • Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus)
  • Patients with only mature teratoma and non-elevated markers upon tumor sampling atdiagnosis
  • Patients who have received any prior tumor-directed therapy for their diagnosis ofGGCT other than surgical intervention and corticosteroids
  • Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology orve evidence of dissemination)
  • Female patients who are pregnant, since fetal toxicities and teratogenic effects havebeen noted for several of the study drugs
    • Note: Serum and urine pregnancy tests may be falsely positive due toHCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant byutional standards
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use anve contraceptive method for the duration of their study participation

Updated on 11 Dec 2024. Study ID: ACNS2021, PHO-COG-ACNS2021, 12475
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