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

Study ID
ACNS1123

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Ryan Carstens
214/648-4916
ryan.carstens@childrens.com

Principal Investigator
Daniel Bowers

Official Title

Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT)

Brief Overview


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.

Summary


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.

Participant Eligibility


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.