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

Official Title

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

Summary:

Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide work in different ways to stop the growth of tumour cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill tumour cells. Giving chemotherapy with radiation therapy may kill more tumour 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 tumours.

Trial Description

Primary Outcome:

  • 3-year PFS rate with NGGCT
  • PFS distribution of localized CNS germinoma
  • Neurocognitive function using the ALTE07C1 protocol
Secondary Outcome:
  • Estimation of the PFS distribution of patients with NGGCT treated with IFR
  • Estimation of the OS distribution of patients with NGGCT treated with IFR assessed
  • 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
  • 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
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 tumour (NGGCT) who have a magnetic resonance imaging (MRI) and tumour marker criteria (CSF and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumour markers OR in patients who have less than a PR after induction chemotherapy with negative tumour 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 behavioural 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 multicentre study. Patients are stratified according to localized primary disease (nongerminomatous germ cell tumour [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 radiation therapy once daily (QD) 5 days a week for 6 weeks. Patients with PR, stable disease (SD), or progressive disease (PD) and normalization of tumour levels undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo radiation therapy. 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 radiation therapy QD 5 days a week for approximately 4 weeks. Patients with PR, SD, or PD with normal tumour markers may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumour during surgery undergo radiation therapy. Patients with PR or SD with residual disease (=< 1.5 cm) and suprasellar (> 0.5 cm) or pineal (> 1 cm) involvement and normal tumour markers undergo radiation therapy 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.

View this trial on ClinicalTrials.gov

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Resources

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