1. Lo sviluppo clinico di nab-paclitaxel Discussant: Nicola Silvestris
III Sessione - Il carcinoma del pancreas
Chair: C. Pinto - Moderatori: F. de Braud, A. Falcone
Lo sviluppo clinico di nab-paclitaxel Discussant: Nicola Silvestris
Studio LAPACT
Alberto Sobrero
IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genova

2. Study Title
nab®-paclitaxel (Abraxane®) plus gemcitabine in subjects with locally advanced pancreatic
cancer (LAPC): An international, open- label, multi-center, Phase 2 study (LAPACT).

3. Study Objectives Primary Objective Secondary Objectives
time to treatment failure (TTF) in induction therapy
followed by Investigator’s Choice of treatment
Secondary Objectives
Disease control rate (DCR) after the first 6 cycles
ORR
PFS and OS
Safety profile
QoL
Exploratory Objective
Changes in circulating nucleic acids correlate with response

4. Primary Study Endpoints
TTF is first dose of study therapy to
treatment failure.
Treatment failure is discontinuation of study therapy due to disease progression, death (of any cause), or the start of a non- protocol-defined anticancer therapy.
Target 5.1  6.6 mo
N = 110

5. Abraxane 125 mg/m2 + Gemcitabine 1000 mg/m2 on Days 1, 8, and 15
Overall Study Design
Screening for Eligibility (14 Days) (N = 110)
Induction phase
Abraxane 125 mg/m2 + Gemcitabine 1000 mg/m2 on Days 1, 8, and 15
6 cycles (28 day/c)
CT/MRI
If CR, PR, or SD
Investigator’s Choice
Continue Abraxane +
Gemcitabine (PD/tox)
Chemoradiotherapy
Surgical Intervention
CT/MRI
Follow-up Period

6. Inclusion Criteria (1 of 3)
Histologically or cytologically confirmed adenocarcinoma of the pancreas.
Unresectable pancreatic cancer according to radiographic criteria (CT or MRI scans) or exploration:
Superior mesenteric vein and portal vein: occlusion, thrombosis, or encasement extending several centimeters
Superior mesenteric artery: tumor abutment > 180 degrees or thrombosis of artery
Celiac axis: abutment or encasement of the celiac axis
Lymph nodes: involvement
Without distant metastasis as defined by whole body CT scan or MRI.
ECOG performance status of 0 or 1.
Acceptable hematology parameters:
Absolute neutrophil count (ANC) ≥ 1500 cell/mm3
Platelet count ≥ 100,000/mm3
Hemoglobin (Hgb) ≥ 9 g/dL

7. Inclusion Criteria (2 of 3)
Acceptable blood chemistry levels:
AST/ SGOT and ALT/ SGPT ≤ 2.5 x upper limit of normal range (ULN)
Total bilirubin ≤ 1.5 ULN
Alkaline phosphatase ≤ 2.5 x ULN
Serum albumin > 3 g/dL
Serum creatinine ≤ 1.5 ULN

8. Chemoradiation therapy
Chemoradiation therapy consisting of the concurrent use of capecitabine or gemcitabine with radiation according to institutional practice
*M - institution treatment plans need to be recorded in source documents to assess if patient completes the Chemoradiation (with start & stop dates)

9. Table of Events – Induction: Abraxane Plus Gemcitabine (1 of 2)
Assessment
Reference to Protocol Section
Screening/ Baseline
Treatment Period Every 28-day Cycle
Follow-Up Period
Day -14 to
Day -1
Day 1
( ±2 days)
Day 8
(±1
days)
Day 15
Every 56 days
(-3/+7
(starting C1D1)
28-day Follow-up Visit (after last dose of IP)
Survival Follow- Up Every 90 Days (± 14 Days)
Informed Consent
Section 6 X -
Medical History, Prior Medication
and Procedures
Sections
6.1, 6.5
Demographics
Section 6.2
AbraxaneAdministration/Accountability
Section 4.1.1
Gemcitabine Administration/Accountability
Physical Examination
Section 6.3
Will be done as per standard of care during the study and as clinically indicated
Vital Signs
Section 6.4
Pregnancy Test (Serum)
Section 6.6
Pregnancy Test (Urine)
CT Scan and Any Other Studies Required for Tumor Imaging
Section 6.7
Height
Section 6.8
Weight

10. Study Efficacy Induction phase CT/MRI scan with/with-out contrast:
every 56 days (-3/+7 days)
Investigator’s Choice Part
every 56 days (-3/+7 days) and 28-day Follow-up Visit (after the last dose of IP and chemoradiation), and post surgery.
*Scans will be done every 56 days (-3/+7 days) until disease progression, withdrawal of consent, lost to follow-up, death (of any cause), or the start of a non-protocol-defined anticancer therapy.

11. Quality of Life Questionnaires
QLQ-C30 and QLQ-PAN26 at:
Screening
Day 1 of every cycle of A+G
28 Day F/U during the nab-Paclitaxel plus Gemcitabine induction phase and during the Investigator’s choice period.

12. Pharmacogenomic Analyses:
Blood sampling for pharmacogenomic analyses:
Collected prior to administration of IP, chemoradiation and/or surgery for ALL subject that undergo surgery as an Investigator’s Choice: just prior to surgery
Kit by sponsor/Covance Ship to Covance
Tumor tissue for molecular profiling:
For All pts that undergo surgery:
Surgical specimen formalin-fixed, paraffin-embedded (FFPE) block ort least 15 slides
surgical pathology report for the tumor should be sent with the tissue.
Samples will be ship to Covance