PEGPH20, Gemicitabine and Nab-Paclitaxel for Pancreatic Ductal Adenocarcinoma
Status:
Terminated
Trial end date:
2018-05-18
Target enrollment:
Participant gender:
Summary
We will be conducting a Phase II study investigating PEGPH20 in combination with gemcitabine
and nab-paclitaxel in patients with borderline resectable pancreatic ductal adenocarcinoma
(PDAC) at the Helen Diller Family Comprehensive Cancer Center at University of California,
San Francisco (UCSF). There are multiple definitions of borderline resectable PDAC including
the MD Anderson definition and the criteria developed during the Consensus Conference
sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology,
and Society for Surgery of the Alimentary Tract. Borderline resectable PDAC cases will be
identified per the definition developed in the currently running inter-group pilot trial for
borderline resectable pancreatic cancer (NCT01821612). Per this trial, borderline resectable
PDAC is defined as "presence of any one or more of the following on CT:
- An interface between the primary tumor and the superior mesenteric vein or portal vein
(SMV-PV) measuring ≥ 180° of the circumference of the vessel wall
- Short-segment occlusion of the SMV-PV with normal vein above and below the level of
obstruction that is amenable to resection and venous reconstruction
- Short segment interface (of any degree) between tumor and hepatic artery with normal
artery proximal and distal to the interface that is amenable to resection and
reconstruction.
- An interface between the tumor, and Superior mesenteric artery (SMA) measuring < 180º of
the circumference of the vessel wall.
This trial will be conducted in two parts. In Part I, pre-treatment endoscopic ultrasound
(EUS)-guided core biopsies of the pancreatic tumor, CA 19-9 levels and functional MRIs
including Dynamic contrast-enhanced (DCE)-MRI and Diffusion-weighted magnetic resonance
imaging (DWI-MRI) will be obtained for the first fifteen patients enrolled. After a 1-week
run-in period with PEGPH20 on days 1 and 4, patients will have repeat EUS-guided core
biopsies, functional MRI, CA 19-9 level and baseline CT chest, abdomen and pelvis.
Subsequently, patients will be started on treatment with PEGPH20, gemcitabine and
nab-paclitaxel given weekly for 3 weeks, every 28 days. To evaluate the disease response to
treatment, CA 19-9 levels will be checked monthly and restaging CT chest, abdomen and pelvis
will be obtained every 8 weeks. If there is disease progression at any point in the study,
patients will be taken off of study and alternative treatments will be offered. At the
completion of 4 cycles of therapy, restaging CT scans will be obtained to determine
resectability. If the patients are found to have resectable disease, an additional functional
MRI will be obtained to evaluate the PDAC stroma. If the patients are able to have successful
surgeries, tissue analyses will be performed on the resected pancreatic tumor. These patients
will then proceed to get 2 cycles of adjuvant chemotherapy with gemcitabine and
nab-paclitaxel. If the patients are deemed to be surgical candidates but are found to have
unresectable disease in the operating room, an intraoperative core biopsy of the pancreatic
tumor will be obtained for tissue analyses. At the time of initiation of therapy with
PEGPH20, patients will be started on prophylactic dose of enoxaparin 1 mg/kg subcutaneous
daily. This will be continued throughout the study participation.
In Part II, an additional 21 patients will be enrolled, and will begin neoadjuvant therapy
with PEGPH20, gemcitabine and nab-paclitaxel without the 1 week run-in of PEGPH20-only or the
pre- and post-run-in EUS-guided biopsies.