In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
The study is a prospective, non-randomized open-label concurrent control study of NovoTTF-100A in recurrent GBM
patients. A prospective, international, multi-center study, will include 30 centers in the US, EU and Israel, at least 15 centers in the US.
The study will include 2 groups: an Investigational Group composed of patients treated with the NovoTTF-100A and a Control Group of concurrent best standard of care chemotherapy. Patients in the NovoTTF-100A group will be treated continuously until disease progression and then followed by telephone interview until death. Minimal recommended treatment duration is 4 weeks and minimal recommended treatment compliance is 18h/day (monthly average).
Study Population Description
The NovoTTF-100A System is intended as a treatment for adult patients (22 years of age or
older) with histologically-confirmed glioblastoma multiforme (GBM), following histologically- or radiologically-confirmed recurrence in the supra-tentorial region of the brain after receiving chemotherapy.
NovoTTF-100A Group - Patients treated with the NovoTTF-100A - Patients will be treated continuously until disease progression - Minimal recommended treatment duration - 4 weeks - Minimal recommended treatment compliance - 18h a day (monthly average)
Control Group - Concurrent best standard of care chemotherapy (control) group
30 centers in the US, EU and Israel. At least 15 centers in the US.
N1=243 NovoTTF-100A patients Comparator arm: N2=243 Concurrent best standard of care control patients
Definitions: λ1 = hazard of death in the test arm λ2 = hazard of death in the comparator arm Primary Statistical Hypothesis: H0: λ1 / λ2 > 1.375 H1: λ1 / λ2 ≤ 1.375 Assumptions: Type I error: 0.05 Power: 0.80 Test statistics: Log-rank test Lost to follow-up: 10%
Primary - Overall survival (months)
Secondary - Change in neuro-cognitive function from baseline based on the
MMSE - Genetic profiling of tumors and correlation with response to NovoTTF-100A treatment, specifically: o MGMT promoter methylation status o EGFR amplification, over expression or rearrangement o Chromosomes 1p/19q deletion status o IDH1 mutation - Adverse event incidence by body system and term, including: o Incidence of seizures and headaches o Anticonvulsant use
Followup Visits and Length of Followup
- Recruitment: 48 months - Follow-up: 12 months from recruitment of last patient - NovoTTF-100A treatment until
clinical disease progression. - Patients will continue to be followed until death Baseline: - Eligibility assessment - MMSE - Genetic profiling of tumor tissue - Adverse event symptoms - Concomitant medication Monthly until clinical disease progression: - Vital status - MMSE - Adverse event record - Concomitant medication (including steroid and anticonvulsant dosing) - Evaluation of progression Monthly after disease progression: - Vital status