Adenocarcinoma Clinical Trial
Official title:
Perioperative Stromal Depletion Strategies in Pancreatic Ductal Adenocarcinoma
Verified date | December 2019 |
Source | University of California, San Francisco |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 3 |
Est. completion date | May 18, 2018 |
Est. primary completion date | May 18, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Greater than or equal to 18 years old - Histologically confirmed pancreatic adenocarcinoma - Borderline resectable disease - Performance status of Eastern Cooperative Oncology Group (ECOG) of 0-1 - Therapy naïve - Evaluable disease with either: - RECIST-defined measurable disease - An elevated serum CA19-9 >100 u/ml - Adequate organ function including: - Bone marrow: Absolute Neutrophil Count (ANC) =1500/mm3, platelets =100,000/mm3 and hemoglobin = 9 g/dL - Hepatic: Serum total bilirubin =1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) and aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT) = 2.5 x ULN. - Renal: Serum creatinine (sCr) = 1.5 x ULN, or creatinine clearance (Ccr) = 40 mL/min as calculated by the Modified Cockcroft-Gault formula. - Peripheral neuropathy < grade 2 - Alkaline phosphatase = 2 times the ULN unless bone metastasis is present in the absence of liver metastasis Exclusion Criteria: - Age younger than 18 years old - Locally advanced or metastatic disease - Known allergy to hyaluronidase - Contraindications to prophylactic dose low molecular weight heparin (LMWH) , including - Patients with recent gastrointestinal bleeding - History of heparin induce thrombocytopenia on LMWH - Subjects with previous severe hemorrhagic events on LMWH - Known contraindications to heparin including: - Recent central nervous system bleed, intracranial or spinal lesion at high risk for bleeding - Active bleeding (major): more than 2 units transfused in 24 hours - Spinal anesthesia/lumbar puncture within the past month - Chronic, clinically significant measurable bleeding > 48 hours - Severe platelet dysfunction (uremia, medications, dysplastic hematopoiesis) - Recent major operation at high risk for bleeding - Underlying hemorrhagic coagulopathy High risk for falls (head trauma) - Presence of metal biliary stents (plastic biliary stents are not an exclusion) - Known status of HIV which is not well-controlled at the time of study eligibility - Untreated Hepatitis B infection - Active infection or antibiotics within 48 hours prior to study - Currently active second primary malignancy or history of malignancy less than 5 years prior to the time of study eligibility (Patients with history of skin cancers excluding melanoma will be eligible for participation). - Serious medical comorbidities such as New York Heart Association Class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months. - Patients with aneurysm clips, ear implants, spinal nerve stimulators, pacemaker, shrapnel or any other metal in their body (contraindication for MRI scans) - Known, existing uncontrolled coagulopathy. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation are eligible IF: they are appropriately anticoagulated and have not had a Grade 2 or greater bleeding episode in the 3 weeks before Day 1. - Current use of warfarin (patients will be eligible if warfarin is discontinued and low-molecular weight heparin is used instead). - Intolerance to dexamethasone - Prior history of cerebrovascular accident or transient ischemic attack, or pre-existing carotid artery disease. - Known pregnancy, nursing women or positive pregnancy test. - Any condition that would preclude informed consent, consistent follow-up and compliance for the study participation. |
Country | Name | City | State |
---|---|---|---|
United States | University of California, San Francisco | San Francisco | California |
Lead Sponsor | Collaborator |
---|---|
Andrew Ko |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of Clinically Relevant Pancreatic Fistula | Our study will be investigating only clinically relevant pancreatic fistulas, i.e. grades B or C. Descriptive statistics will be used report the incidence of pancreatic fistula within the 7-day post-operative period after neoadjuvant treatment | Up to 5 years | |
Primary | Rate of Pathologic Complete Response (pCR) | Descriptive statistics with frequency / proportion will be used to evaluate rate of pathologic complete response using the pathological exam of resected tumors. pCR was defined as area of scarring in pancreatic parenchyma and/or peripancreatic soft tissue with chronic inflammation, with or without acellular mucin pools and histiocytic infiltrates, but no residual viable invasive adenocarcinoma cells in the pancreatectomy specimen | Up to 5 years | |
Secondary | Percent Change of CA19-9 Response Rate | To evaluate the disease response to treatment, CA19-9 levels will be measured every 4 weeks and restaging Computerized tomography (CT) / magnetic resonance imaging (MRI)of the chest, abdomen and pelvis will be obtained every 8 weeks | Up to 5 years | |
Secondary | Margin-Negative (R0) Resection Rate | Patients will be evaluated for surgical resection depending on imaging obtained on Cycle 4 Day 21. R0 Resection rate determined by CA 19-9 levels will be checked every 4 weeks and restaging CT/MRI of the chest, abdomen and pelvis will be obtained every 8 weeks surgical resection if the patient's tumor is deemed resectable post-therapy. Patients who have received at least 2 complete, 28-day cycles of study drugs were included in the secondary analyses | Up to 5 years | |
Secondary | Overall Response Rate (ORR) | Descriptive statistics with frequency and proportion of overall response determined by CA 19-9 levels will be checked every 4 weeks and restaging CT/MRI of the chest, abdomen and pelvis will be obtained every 8 weeks | Up to 5 years | |
Secondary | Disease Free Survival (DFS) | Kaplan-Meier methods will be used to analyze disease free survival and median time and 95% confidence intervals will be reported | Up to 5 years |
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