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PEGPH20, Gemicitabine and Nab-Paclitaxel for Pancreatic Ductal Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT02487277
Recruitment Status : Recruiting
First Posted : July 1, 2015
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
Andrew Ko, University of California, San Francisco

Brief Summary:

We will be conducting a Phase II study investigating PEGPH20 in combination with gemcitabine and nab-paclitaxel in patients with borderline resectable PDAC at the Helen Diller Family Comprehensive Cancer Center at 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 SMA measuring < 180º of the circumference of the vessel wall.

This trial will be conducted in two parts. In Part I, pre-treatment EUS-guided core biopsies of the pancreatic tumor, CA 19-9 levels and functional MRIs including DCE-MRI and 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.


Condition or disease Intervention/treatment Phase
Adenocarcinoma Drug: PEGPH20 Drug: Gemcitabine Drug: Nab-paclitaxel Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Perioperative Stromal Depletion Strategies in Pancreatic Ductal Adenocarcinoma
Actual Study Start Date : July 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: Run-In
PEGPH20: 3ug/kg on Days 1 and 4
Drug: PEGPH20
Experimental: Treatment
PEGPH20: 3ug/kg on Days 1, 8, 15 Gemcitabine: 1000mg/m^2 on Days 1, 8, 15 Nab-paclitaxel: 125mg/m^2 on Days 1, 8, 15
Drug: PEGPH20
Drug: Gemcitabine
Drug: Nab-paclitaxel



Primary Outcome Measures :
  1. Clinically Relevant Pancreatic Fistula [ Time Frame: Up to 5 years ]
  2. Pathologic Complete Response [ Time Frame: Up to 5 years ]
    Measured by pathological exam of resected tumors


Secondary Outcome Measures :
  1. CA19-9 Response Rate [ Time Frame: Up to 5 years ]
    Tumor marker testing

  2. R0 Resection Rate [ Time Frame: Up to 5 years ]
  3. Overall Response Rate [ Time Frame: Up to 5 years ]
    Measured by imaging studies

  4. Disease Free Survival [ Time Frame: Up to 5 years ]
    Measured by imaging studies



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Greater than or equal to 18 years old
  • Histologically confirmed pancreatic adenocarcinoma
  • Borderline resectable disease
  • Performance status of 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: ANC ≥1500/mm3, platelets ≥100,000/mm3 and hemoglobin ≥ 9 g/dL
  • Hepatic: Serum total bilirubin ≤1.5 x upper limit of normal (ULN), ALT
  • (SGPT) and AST (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 ≤ 2X 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02487277


Contacts
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Contact: Andrew Ko, MD 415-353-7286 Andrew.Ko@ucsf.edu
Contact: Julie Sudduth-Klinger 415-353-7463 Julie.Sudduth-Klinger@ucsf.edu

Locations
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United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94158
Contact: Elizabeth Dito, RN    415-353-7244    Elizabeth.Dito@ucsf.edu   
Contact: Anna Ong, RN    415-885-7603    Anna.Ong@ucsf.edu   
Sponsors and Collaborators
Andrew Ko

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Responsible Party: Andrew Ko, Professor of Clinical Medicine, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02487277     History of Changes
Other Study ID Numbers: 144515
First Posted: July 1, 2015    Key Record Dates
Last Update Posted: June 14, 2017
Last Verified: June 2017
Keywords provided by Andrew Ko, University of California, San Francisco:
Pancreatic
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs