Clinical Trial: Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Radiotherapy Alone Versus Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy alone is as effective as chemotherapy plus radiation therapy in treating germ cell tumor.

PURPOSE: This randomized phase III trial is studying radiation therapy alone to see how well it works compared to chemotherapy and radiation therapy in treating patients with newly diagnosed primary CNS germ cell tumor.


Detailed Summary:

OBJECTIVES:

Primary

  • Compare event-free survival and overall survival of patients with newly diagnosed primary CNS germ cell tumor treated with conventional radiotherapy alone (regimen A) vs chemotherapy followed by tumor response-based radiotherapy (regimen B).

Secondary

  • Determine the complete response rate in patients treated with regimen B.
  • Determine the acute and subacute toxicity of regimen B in these patients.
  • Compare treatment-related morbidity, in terms of verbal learning and memory, executive functioning, and quality of life, in patients treated with these regimens.
  • Determine the prognostic value of baseline serum, lumbar, and intraventricular levels of human chorionic gonadotropin levels from patients treated with these regimens.
  • Determine the prognostic value of extent of disease (M+ vs modified M+ vs M0) on event-free survival and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor location (pineal vs suprasellar vs pineal + suprasellar or other), and disease stage (disseminated vs occult multi-focal vs localized). Patients are randomized to 1 of 2 treatment regimens.

All patients undergo an operative procedure (endoscopic biopsy, stereotactic biopsy, or open craniotomy) to confirm the diagnosis of pure germ cell germinoma followed by an intraoperative and perioperative staging evaluation.

    Data will be summarized as number of patients in the following categories at the time of data cutoff for analyses of 3-year EFS: 1)Experienced a qualifying event (QE) (see below);2)Event-free through 3 years of follow-up;3)Event-free until data cutoff (if less than 3 years of follow-up);4)Withdrew from study;5)Lost to follow-up.

    QEs: 1)disease progression, defined as increase >= 40% in tumor volume or >= 25% in tumor area of target lesions;2)development of new lesions;3)occurrence of a second malignant neoplasm, defined as a malignancy with different histological type from trial-qualifying diagnosis;4)death from any cause.

    Stat. analyses will be based on time from enrollment to the earliest of: 1)occurrence of any of the QEs;2)withdrawal from study or lost to follow-up;3)completion of three years of follow-up event-free;4)data cutoff for completion of the statistical analyses for the protocol's primary objective.

    NOTE: Reported data are through May 2009 (see Caveats section).



Original Primary Outcome:

Current Secondary Outcome:

  • Response [ Time Frame: Up to 5 years ]
  • Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: From the beginning of treatment, assessed up to 5 years ]
    The analysis of toxicity will focus on estimating the rates of key acute and subacute toxicity occurring during the first induction chemotherapy. Estimates will be obtained using life-table methods with an event defined as the first occurrence of a key acute or sub-acute toxicity. Patients who have progression or recurrence of disease will be censored in these analyses. The precision of the estimates of toxicity rate can be approximated by an analysis of binomial proportions.
  • Quality of Life (QOL) and Neurocognitive Assessment (NP) [ Time Frame: Up to 2 years ]
    The primary endpoints for QOL and NP assessments will be the global scale value from each of these instruments at the two-year time point. Analyses of subscales (if they exist) and of assessments at other times will be of secondary interest. It is assumed that scale values are standardized to a reference normal population. Comparisons of each treatment group with the standard population mean, using a two-sided test with Type I error 0.025 (an adjustment for multiple comparison) will be able to detect differences from the standard mean that are 20% smaller.


Original Secondary Outcome:

Information By: Children's Oncology Group

Dates:
Date Received: June 10, 2004
Date Started: January 2007
Date Completion:
Last Updated: February 7, 2017
Last Verified: February 2017