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

TPS9595 General Poster Session (Board #45H), Sun, 8:00 AM-12:00 PM
Intraperitoneal radioimmunotherapy (RIT) for desmoplastic small round
cell tumor (DSRCT). Presenting Author: Shakeel Modak, Memorial Sloan-
Kettering Cancer Center, New York, NY
Background: DSRCT, a rare sarcoma of adolescents and young adults arises
from serosal surfaces typically the peritoneum. It is characterized by
t(11;22)(p13;q12) chromosomal translocation; and is lethal in �80% of
patients despite aggressive surgery and chemoradiotherapy. Disease recurrence
often presents as multifocal peritoneal implants, making it uniquely
suited for intraperitoneal (IP) targeting. Since DSRCT is radiosensitive, we
hypothesize that improving local control with targeted radiotherapy may
reduce relapse and enhance survival. IP RIT, by virtue of prolonged
residence time, and slow/incomplete transfer to the circulation, may
selectively target IP disease while minimizing organ toxicity. The anti-4Ig-
B7H3 murine monoclonal antibody 8H9 binds to 96% of primary DSRCT
with restricted reactivity to normal tissue (Med Pediatr Oncol 39:547).
131I-8H9 targets DSRCT xenografts and has proven safe at 80mCi when
injected intrathecally (J Neurooncol 97:409). 124I-8H9, a novel positronemitting
radioimmunoconjugate is ideally suited for quantitative imaging
and pharmacokinetic (PK) studies. Methods: We have initiated a phase I
study to test the safety of IP RIT using 131I-8H9 in patients with DSRCT
(clinicaltrials.gov NCT01099644). Cohorts of 3-6 patients are treated with
131 2 2 I-8H9 at escalated doses from 30mCi/m -60mCi/m as a single IP
injection. An IP tracer dose of 2mCi124I-8H9 is given prior to 131I-8H9 to
acquire high-resolution PET images and data on 8H9 tumor targeting and
biodistribution. PK is also studied using serial blood draws. Patients are
monitored for toxicity clinically and biochemically. Response to treatment
is assessed using RECIST criteria and via a follow up 124I-8H9 PET scan if
tumor targeting is noted on initial imaging. Hematopoietic stem cells are
harvested a priori to reverse myelosuppression if any. Three cohorts of
patients (n�9) up to 50mCi/m2 have completed therapy thus far without
dose-limiting toxicity or myelosuppression. This is the first study of IP RIT
in pediatrics, and the first to use PET for IP RIT. Data obtained will be
critical in establishing safety of IP 131I-8H9 in children and young adults,
and in designing phase II trials to study efficacy of IP RIT for DSRCT.
TPS9597^ General Poster Session (Board #46B), Sun, 8:00 AM-12:00 PM
The BERNIE study: A phase II study evaluating addition of bevacizumab
(Bv) to chemotherapy in children and adolescents with metastatic rhabdomyosarcoma
(mRMS) and non-rhabdomyosarcoma soft tissue sarcoma
(mNRSTS). Presenting Author: Julia C. Chisholm, The Royal Marsden NHS
Foundation Trust, Sutton, United Kingdom
Background: Despite therapeutic advances, patient outcomes in mRMS and
mNRSTS remain poor. The phase I study (Glade-Bender et al., J Clin Oncol.
2008) indicated that Bv is well tolerated in children with refractory solid
tumors and yielded pharmacokinetic (PK) data that support further studies
of Bv in childhood cancer. Reports of Bv used in children with solid tumors
showed safety profiles consistent with data from adults. Methods: In this
phase II trial, 150 patients aged 6 months to 18 years who present with
mRMS or mNRSTS are randomized to receive 18 months of standard
combined modality therapy as per EpSSG guidelines, either alone or with
Bv. Treatment consists of 2 phases: induction therapy [9 three-weekly
cycles including 4 cycles of IVADo (ifosfamide, vincristine, actinomycin D,
and doxorubicin), followed by 5 cycles of IVA (i.e., without doxorubicin)]
and maintenance therapy (12 four-weekly cycles of vinorelbine and
cyclophosphamide). Local therapy is considered after the 6th induction
cycle. Primary endpoint is event-free survival (EFS). PK sampling is
performed on all patients randomized to the experimental arm during the
first 4 cycles of induction. After the primary efficacy and safety analysis, all
patients who have not met the primary endpoint are followed for at least 47
months for survival and long-term effects of treatment. The study enrolled
75 patients between July 2008 and January 2012; 37 patients discontinued
study treatment (including 17 patients who died, all due to disease
progression) and 9 patients have completed study treatment.
Pediatric Oncology
629s
TPS9596 General Poster Session (Board #46A), Sun, 8:00 AM-12:00 PM
The HERBY study: A phase II open label, randomized, multicenter,
comparative study of bevacizumab (Bv)-based therapy in pediatric patients
with newly diagnosed supratentorial high-grade glioma (HGG). Presenting
Author: Jacques Grill, Institut Gustave Roussy, Villejuif, France
Background: Despite therapeutic advances, outcomes in pediatric HGG
remain poor. The phase I study (Glade-Bender et al., J Clin Oncol. 2008)
indicated that Bv is well tolerated in children with refractory solid tumors
and yielded pharmacokinetic (PK) data that support further studies of Bv in
childhood cancer. Reports of Bv used in children with solid tumors showed
safety profiles consistent with data from adults. Methods: 120 evaluable
patients aged 3-18 years with newly diagnosed histologically confirmed
WHO grade 3or 4 HGG are randomized to receive standard combined
modality therapy as currently adopted worldwide by the pediatric neurooncology
community with or without Bv. Treatment consists of 6 weeks of
concomitant TMZ and local radiotherapy, followed by a 4-week TMZ
treatment break and 48 weeks of adjuvant TMZ with or without Bv every
other week. Primary endpoint is event-free survival (EFS). Progression is
based on RANO criteria. Secondary endpoints are overall survival (OS),
safety, feasibility, and tolerability. PK sampling is performed during cycles
1-4 of the adjuvant TMZ phase on all patients randomized to receive Bv.
Health-related quality of life, neurocognitive functions, MGMT methylation
status, functional changes in tumor based on magnetic resonance diffusion
& perfusion imaging and spectroscopy are explored as well as the
correlation of biomarkers with clinical activity and adverse events. All
randomized patients will be followed for at least 3 years. Analysis of EFS
and secondary endpoints will be performed after the 120 patients evaluable
for EFS have been followed for 1 year. Multimodal imaging will provide
a platform to develop new imaging criteria for pediatric neuro-oncological
treatment response. An updated OS and safety analysis will be performed 3
years after the last patient has been randomized. The first patient was
randomized in October 2011; completion of the study is expected in 2016.
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