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

272s Gastrointestinal (Noncolorectal) Cancer
TPS4136 General Poster Session (Board #52G), Mon, 8:00 AM-12:00 PM
Gemcitabine with nab-paclitaxel in neoadjuvant treatment of pancreatic
adenocarcinoma: GAIN-1 study. Presenting Author: Neelam Vijay Desai,
University of Florida, Gainesville, FL
Background: Pancreatic adenocarcinoma remains a deadly disease with a
dismal prognosis. Only 15% of patients present with resectable disease
with 5-year survival only 20% despite adjuvant therapy. Neoadjuvant
treatment may improve R0 resection rates, allows more patients curative
surgery, is cost effective, and may improve overall survival by incorporating
earlier systemic therapy. Methods: This is a prospective single arm
open-label phase II trial using gemcitabine (G) and nab-paclitaxel (A) in the
neoadjuvant treatment of resectable and borderline-resectable pancreatic
cancer. Patients are stratified by risk group as defined by a predictive model
published by Bao et al and the NCCN expert consensus statement (Table):
low-risk resectable (Group 1) and high-risk resectable or borderlineresectable
(Group 2). Group 1 receives 3 cycles of G�A then surgical
resection. 1 cycle � G 1000mg/m2 �A 100mg/m2 IV on Days 1, 8, 15 Q28
days. Group 2 receives 2 cycles of G�A followed by 2 weeks of hypofractionated
IMRT (50.4Gy in 10 fx) with G 400mg/m2 IV weekly, then surgical
resection. The primary endpoints are R0 resection rate and overall response
rates. Secondary endpoints are PFS, OS, 30-day post-op mortality, toxicity,
QOL and molecular analysis including DPC4 and SPARC levels in tumor
and stroma. Enrollment has just begun with a total accrual goal of 60
patients. This platform will allow targeted systemic therapy and tailored
treatment stratification to optimize outcomes in curable pancreatic cancer.
This study is registered with Clinicaltrials.gov (NCT01470417).
Risk stratification Definition
Low-risk -EUS Stage � IA OR
-No vascular involvement on CT &
a. EUS stage IB or IIA OR
b. EUS stage � IIB but tumor � 2.6cm
High-risk -EUS stage IB or IIA but vascular involvement on CT
-No vascular involvement but EUS stage � IIB & tumor � 2.6 cm
-(�) nodes on PET or FNA
Borderline -Involvement of SMV/portal vein but w/o encasement of arteries, or
short segment venous occlusion 2/2 tumor thrombus
or encasement but w/ suitable vessels to allow
resection & reconstruction
-Gastroduodenal artery encasement up to hepatic artery
w/ short segment involvement of hepatic artery,
w/o extension to celiac axis
-Tumor abutment of SMA �180 degrees of vessel wall
TPS4138 General Poster Session (Board #53A), Mon, 8:00 AM-12:00 PM
PaFLO: Pazopanib with 5-fluorouracil, leucovorin, and oxaliplatin (FLO) as
first-line treatment in advanced gastric cancer: A randomized phase II
study of the Arbeitsgemeinschaft internistische Onkologie (AIO). Presenting
Author: Kirstin Breithaupt, Charité-Universitätsmedizin Berlin, Campus
Virchow-Klinikum, Med Klinik m. S. Hämatologie u. Onkologie, Berlin,
Germany
Background: VEGF inhibition in gastric cancer shows promising improvement
of remission rate and progression-free survival (Ohtsu et al., JCO
2011). Pazopanib is an orally available tyrosine kinase inhibitor (TKI)
selectively inhibiting VEGFR-1, -2, -3, c-kit and PDGFR. It is approved for
treating renal cell cancer. A phase-I trial showed good tolerability of
pazopanib with full-dose FOLFOX in solid tumors (Brady et al., ASCO,
2009). FLO is a widely used combination for advanced gastric cancer
recommended in national guidelines. Methods: 75 Patients with HER-2negative
locally advanced or metastatic adenocarcinoma of the stomach or
the gastro-esophageal junction will be randomized in a 2:1 ratio to A: FLO
(F 2600mg/m2 as 24h infusion, L 200mg/m2, O 85 mg/m2) d1 �
pazopanib (800mg) d1-14 and B: FLO; repeated for 12 2-week cycles,
followed by a maintenance therapy with pazopanib alone in A and an
observation period in B until disease progression. Primary endpoint is
progression-free survival rate (PFSR) at 6 months, secondary endpoints are
PFSR at 9 and 12 months, median PFS, response rate, duration of
response, toxicity, tolerability and overall survival. Additionally, we evaluate
the predictive and prognostic relevance of PIGF, VEGF, and the
respective soluble receptors sVEGFR1 and sVEGFR2 as biomarkers for
clinicopathological parameters, clinical response to treatment and tumor
volume change. Based on a phase-III trial demonstrating a 6-month PFSR
of 44% with FLO (Al-Batran et al., 2008), we estimate a 6-month PFSR of
55% in the experimental group. Given an alpha error of 0.1 and a beta error
of 0.2 in a Simon 2-stage minimax design, in the first stage �12 of 30
patients need to be progression free at 6 months to continue and after the
second stage �25 of 50 patients should be progression free at 6 months to
justify further evaluation. Randomization is performed to estimate selection
bias according to pazopanib-specific exclusion criteria for comparison
with historical data. Study protocol received ethics committee approval in
November 2011 and is currently recruiting patients in 15 AIO centers.
TPS4137 General Poster Session (Board #52H), Mon, 8:00 AM-12:00 PM
PAN1: A randomized phase II study evaluating potential predictive biomarkers
in the treatment of metastatic pancreatic cancer. Presenting Author: Yu
Jo Chua, Medical Oncology Unit, The Canberra Hospital, Garran, Australia
Background: Biomarker-based selection of cancer treatments has already
entered routine clinical practice in some cancer types. Recent retrospective
data suggests the human equilibrative nucleoside transporter 1 (hENT1) to
be promising predictive marker for benefit from gemcitabine in pancreatic
cancer, at least in resected disease. Methods: 80 patients will be randomised
to receive either gemcitabine or FOLFOX chemotherapy (folinic
acid (FOL) fluorouracil (F) and oxalipatin (OX)) with stratification based on
hENT1 status. All patients will be required to have tumour samples tested
for hENT1 prior to randomisation, with both hENT1 positive and negative
patients eligible for inclusion. Patients will continue their assigned
treatment until progression, or unacceptable toxicity. Primary endpoint:
Progression free survival in each chemotherapy arm (FOLFOX/gemcitabine).
Secondary endpoints: efficacy/activity of gemcitabine and FOLFOX
as assessed by OS (overall survival), TTP (time to progression), RR
(response rate according to RECIST v1.1), CA19.9 response; Percentage of
eligible patients able to be randomised within 14 days of screening; PFS in
each biomarker-selected cohort (hENT1 positive/negative); Treatment
related toxicity in each chemotherapy group (CTCAE v4.0) and in biomarker
cohorts (hENT1 positive/negative); establishment of a tissue bank from
patients treated with and without gemcitabine for further biomarker
studies. Eligibility: Adult patients with radiologically and histologically
confirmed metastatic pancreatic adenocarcinoma who have not previously
received treatment for metastatic disease, and who have tumour tissue
available for hENT1 testing are eligible for the study. Patients who do not
have tumour tissue available will be required to undergo core biopsy to
obtain tissue for hENT1 testing. Status: Opened to accrual July 2011.
TPS4139 General Poster Session (Board #53B), Mon, 8:00 AM-12:00 PM
A randomized, multicenter, double-blind, placebo (PBO)-controlled phase
III study of paclitaxel (PTX) with or without ramucirumab (IMC-1121B;
RAM) in patients (pts) with metastatic gastric adenocarcinoma, refractory
to or progressive after first-line therapy with platinum (PLT) and fluoropyrimidine
(FP). Presenting Author: Hansjochen Wilke, Kliniken Essen Mitte
Center of Palliative Care, Essen, Germany
Background: Vascular endothelial growth factor (VEGF) expression in gastric
cancer (GC) is associated with more aggressive clinical disease. VEGF
expression in resected GC is associated with tumor recurrence and shorter
survival. Data from Phase 2 and 3 studies suggest that agents targeting the
VEGF pathway improve the efficacy of some chemotherapy regimens in 1stand
2nd-line treatment of patients with gastric or gastroesophageal
carcinomas. RAM, a fully human monoclonal antibody, binds to the VEGF
receptor-2 (VEGFR-2), potently blocks the binding of VEGF to VEGFR-2,
inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGFinduced
mitogenesis of human endothelial cells. Methods: Pts are randomized
1:1 to receive PTX � RAM or PTX � PBO until disease progression or
intolerable toxicity (28-day cycle; RAM/PBO 8 mg/kg Days 1, 15; PTX 80
mg/m2 Days 1, 8, 15). Eligibility includes metastatic or locally advanced,
unresectable gastric or gastroesophageal junction adenocarcinoma; prior
first-line therapy with any PLT/FP doublet with or without anthracycline;
progressive disease during or following first-line therapy; ECOG PS 0-1;
bilirubin � 1.5 � upper limit of normal (ULN), transaminases � 3 � ULN
for ALAT/ASAT if no liver metastases, � 5 � ULN if liver metastases;
creatinine � 1.5 � ULN; absolute neutrophil count � 1.5 � 109 /L,
hemoglobin � 9 g/dL; platelets � 100 � 109 /L. The primary endpoint is
overall survival (OS). Secondary endpoints include progression-free survival,
time to progression, best overall response, objective response rate,
safety, patient-reported outcome measures, pharmacodynamics, immunogenicity,
and pharmacokinetics. This study, powered at 90% to show an
increase in OS (mdn: 7mPTX�PBO, 9.33 m PTX � RAM) at a 1-sided
2.5% significance level, will randomize 663 pts. As of 18 January 2012,
approximately 58% of planned pts were randomized. The IDMC reviewed
this study 23 June and 01 December 2011 and recommended the study
continue unmodified.
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