Annual Meeting Proceedings Part 1 - American Society of Clinical ...

TPS2106 General Poster Session (Board #20E), Sat, 1:15 PM-5:15 PM
Phase III trial of tumor-treating fields (TTFields) together with temozolomide
compared with temozolomide (TMZ) alone in patients with newly
diagnosed glioblastoma multiforme (NCT00916409). Presenting Author:
Santosh Kesari, University of California, San Diego, San Diego, CA
Background: TTFields therapy is a novel, non-invasive, anti-mitotic treatment,
inhibiting tumor growth by interfering with the metaphase to
anaphase transition during mitosis (Lee et al., 2011). TTF therapy was
recently approved by the FDA for recurrent GBM following a prospective,
randomized trial. Preclinical studies have shown TTFields and TMZ to have
an additive inhibitory effect on glioma cell proliferation. The design for the
current study was supported by results from a pilot study with TTFields
therapy and TMZ in patients with newly diagnosed GBM demonstrating
favorable safety, tolerability and promising efficacy (Kirson et al., 2009).
Methods: The hypothesis of the current study is that the addition of
TTFields therapy to maintenance TMZ will increase progression free
survival (PFS) of newly diagnosed GBM patients. Secondary endpoints
include overall survival (OS), radiological response, quality of life and
safety. Eligible patients will be randomized (2:1) to continuous TTFields
therapy (200 kHz) in combination with maintenance TMZ versus maintenance
TMZ alone. Maintenance TMZ will be administered as per the Stupp
Protocol for 6 courses (Stupp et al., 2005). TTFields therapy may be
administered for up to 24 months. Patients will be stratified based on:
extent of resection and MGMT methylation status. Eligibility criteria
include: pathological diagnosis of GBM; Karnofsky � 70; previous chemoradiotherapy
per Stupp Protocol; no progressive disease at baseline.
Patients with infratentorial tumor or implanted electronic devices are
excluded. The sample size of 700 patients will have 80% power to detect a
2 month (9 vs 7 months) improvement in PFS using log-rank test with an
overall 5% 2-sided type I error. The trial is also powered to detect a 4.5
month increase in median OS in NovoTTF-100A/TMZ patients. Patients
will be followed clinically monthly and with bimonthly MRI to assess tumor
progression and additional endpoints. 221 patients have been enrolled at
the time of abstract submission. The DMC last reviewed the trial in October
2010 and recommended that the trial continue as designed.
Central Nervous System Tumors
141s
TPS2107 General Poster Session (Board #20F), Sat, 1:15 PM-5:15 PM
A randomized, double-blind, controlled phase IIb study of the safety and
efficacy of ICT-107 in newly diagnosed patients with glioblastoma multiforme
following resection and chemoradiation. Presenting Author: Elma S.
Hawkins, Immunocellular Therapeutics, Ltd., Woodland Hills, CA
Background: Tumor stem cells have been correlated with recurrence and
clinical outcome in glioblastoma multiforme (GBM). ICT-107 is an autologous
vaccine consisting of the patient’s dendritic cells pulsed with 6
synthetic peptide CTL epitopes targeting the GBM tumor and tumor-stem
cell associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100 and
IL-13R�2. Phase I results showed a good safety profile and interesting
clinical potential (ASCO, 2010, abs#2097 and ASCO, 2011, abs#2042)
in 16 newly diagnosed GBM patients with a median progression-free
survival (PFS) of 16.9 months (measured from surgery) and a median
overall survival (OS) of 38.4 months. Methods: In this Phase II study eligible
patients have newly diagnosed GBM and complete surgical resection or
minimum residual tumor � 1cm3 , are HLA-A1 and/or HLA-A2 positive,
older than 18, have Karnofsky Performance Score (KPS) of � 70% and
have adequate hematologic and chemistry parameters. Patients with a
serious immune or autoimmune disorder or other systemic disease are
excluded. Patients undergo apheresis to isolate peripheral blood mononuclear
cells (PBMCs) to be used for preparation of study treatment (ICT-107
and Control). Pre-study treatment consists of 6 weeks of concurrent
temozolomide (TMZ) and radiation. After stratification by site and age,
patients are randomized 2:1 to receive either ICT-107 or its matching
control (autologous, unpulsed dendritic cells). Patients then receive
induction ICT-107 or control once a week for four weeks. All patients
subsequently receive maintenance TMZ for 5 days per month for 12
months. Booster vaccinations occur at Cycles 1, 3, 6 and 10, and every six
months thereafter. The primary endpoint is OS and secondary endpoints
include PFS, rates of OS and PFS at 6 months after surgery and every 3
months thereafter, safety and tolerability of ICT-107, immune response to
ICT-107 and predictors of response. 120 patients have been enrolled in
this ongoing trial. It is expected that approximately 200 patients will be
enrolled for screening with the intention to randomize at least 102 patients.
The trial significance is alpha�0.025 one-sided.
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