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Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma

Primary Purpose

Pancreatic Cancer, Advanced Pancreatic Ductal Adenocarcinoma

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Nab-paclitaxel
PEGPH20
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring Gemcitabine, Nab-paclitaxel, PEGPH20, Rivaroxaban, thromboembolic event (TE), 16-1066

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed, written Institutional Review Board (IRB)-approved Informed Consent Form (ICF).
  • Histologically confirmed locally advanced unresectable (Stage III) or Stage IV PDAC.
  • Measurable or evaluable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST v1.1.
  • For patients with locally advanced disease, no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of PDAC is permitted. For patients with metastatic disease, prior treatment for non-metastatic disease with 5-FU or gemictabine administered as radiation sensitizer, or as a cytotoxic therapy, in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no ≥ Grade 2 treatment-related toxicities are present.
  • Karnofsky Performance Status ≥70%.
  • Life expectancy ≥3 months.
  • Age ≥18 years.
  • A negative serum pregnancy test, if female of reproductive potential.
  • Screening clinical laboratory values as follows, performed within 14 days prior to day 1:

    • Total bilirubin ≤1.5 times upper limit of normal (ULN).
    • Aspartate aminotransferase ([AST]; serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ([ALT]; serum glutamic pyruvate transaminase [SGPT]) ≤2.5 times ULN, (if liver metastases are present, then ≤5 times ULN is allowed).
    • Serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥60 mL/min.
    • Serum albumin ≥3.0 g/dL.
    • Absolute neutrophil count (ANC) ≥1,500 cells/mm3.
    • Platelet count ≥100,000 plt/mm3.
    • Hemoglobin ≥9 g/dL
    • Prothrombin time (PT)/international normalized ratio (INR) within normal limits (±15%) or within therapeutic range if on warfarin.
    • Partial thromboplastin time (PTT) within normal limits (±15%).
  • For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study. Effective contraceptive methods consist of prior sterilization, intra-uterine device, oral or injectable contraceptives, and/or barrier methods. Abstinence alone is not considered an adequate contraceptive measure for the purposes of this study.

Exclusion Criteria:

  • Known central nervous system involvement or brain metastases.
  • New York Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months.
  • Known, clinically significant carotid artery disease.
  • Known, increased risk of bleeding.
  • Patients with TE event occurring > 6months prior to enrollment and receiving active anticoagulation.
  • Patients with any prior history of arterial thrombosis or symptomatic pulmonary embolism.
  • Patients with current use of megestrol acetate (use with 10 days of Day 1) will be excluded.
  • Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
  • Known active infection with human immunodeficiency virus, hepatitis B, or hepatitis C.
  • Known allergy to hyaluronidase.
  • Patients with prosthetic heart valves
  • Women currently pregnant or breastfeeding.
  • Intolerance of dexamethasone.
  • History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer or curatively-treated cervical carcinoma in-situ.
  • History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).
  • Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications.
  • Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for the study.
  • Inability to comply with study and follow-up procedures as judged by the Investigator.

Sites / Locations

  • Hartford Healthcare Cancer Institute @ Hartford Hospital
  • Miami Cancer Institute
  • Memorial Sloan Kettering Basking Ridge
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering Commack
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau
  • Lehigh Valley Health Network

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Patients without a prior thromboembolic event (TE)

Patients with a prior thromboembolic event (TE)

Arm Description

Patients without a prior TE will be treated with prophylactic dose and schedule of rivaroxaban (10 mg QD), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.

Patients with a prior TE will be treated with therapeutic dose and schedule of rivaroxaban (15 mg BID for 21 days for induction if indicated, then 20 mg QD for chronic treatment), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.

Outcomes

Primary Outcome Measures

rate of symptomatic TE events
This includes any grade 2 or grade 3 thromboembolic event as defined by NCI CTCAE v4.0 found on incidental imaging, which would indicate a need for medical intervention.

Secondary Outcome Measures

Full Information

First Posted
September 29, 2016
Last Updated
July 3, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Halozyme Therapeutics, Miami Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02921022
Brief Title
Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma
Official Title
Pilot Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2016 (undefined)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Halozyme Therapeutics, Miami Cancer Institute

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to test any good and bad effects of the study drug called PEGPH20. PEGPH20 alone is considered investigational. The Food and Drug Administration (FDA) has not approved the marketing or sale of PEGPH20, but have authorized its use in research studies with humans. PEGPH20 could shrink the cancer but it also can cause side effects. PEGPH20 is an enzyme that breaks down a specific tissue component called hyaluronan produced by some tumors. Pancreatic tumors often have a large amount of hyaluronan. The removal of hyaluronan from tumors may decrease tumor growth.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Advanced Pancreatic Ductal Adenocarcinoma
Keywords
Gemcitabine, Nab-paclitaxel, PEGPH20, Rivaroxaban, thromboembolic event (TE), 16-1066

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients without a prior thromboembolic event (TE)
Arm Type
Experimental
Arm Description
Patients without a prior TE will be treated with prophylactic dose and schedule of rivaroxaban (10 mg QD), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.
Arm Title
Patients with a prior thromboembolic event (TE)
Arm Type
Experimental
Arm Description
Patients with a prior TE will be treated with therapeutic dose and schedule of rivaroxaban (15 mg BID for 21 days for induction if indicated, then 20 mg QD for chronic treatment), together with standard dose and schedule of gemcitabine, nab-paclitaxel and PEGPH20.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Intervention Type
Drug
Intervention Name(s)
PEGPH20
Primary Outcome Measure Information:
Title
rate of symptomatic TE events
Description
This includes any grade 2 or grade 3 thromboembolic event as defined by NCI CTCAE v4.0 found on incidental imaging, which would indicate a need for medical intervention.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed, written Institutional Review Board (IRB)-approved Informed Consent Form (ICF). Histologically confirmed locally advanced unresectable (Stage III) or Stage IV PDAC. Measurable or evaluable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST v1.1. For patients with locally advanced disease, no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of PDAC is permitted. For patients with metastatic disease, prior treatment for non-metastatic disease with 5-FU or gemictabine administered as radiation sensitizer, or as a cytotoxic therapy, in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no ≥ Grade 2 treatment-related toxicities are present. Karnofsky Performance Status ≥70%. Life expectancy ≥3 months. Age ≥18 years. A negative serum pregnancy test, if female of reproductive potential. Screening clinical laboratory values as follows, performed within 14 days prior to day 1: Total bilirubin ≤1.5 times upper limit of normal (ULN). Aspartate aminotransferase ([AST]; serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ([ALT]; serum glutamic pyruvate transaminase [SGPT]) ≤2.5 times ULN, (if liver metastases are present, then ≤5 times ULN is allowed). Serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥60 mL/min. Serum albumin ≥3.0 g/dL. Absolute neutrophil count (ANC) ≥1,500 cells/mm3. Platelet count ≥100,000 plt/mm3. Hemoglobin ≥9 g/dL Prothrombin time (PT)/international normalized ratio (INR) within normal limits (±15%) or within therapeutic range if on warfarin. Partial thromboplastin time (PTT) within normal limits (±15%). For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study. Effective contraceptive methods consist of prior sterilization, intra-uterine device, oral or injectable contraceptives, and/or barrier methods. Abstinence alone is not considered an adequate contraceptive measure for the purposes of this study. Exclusion Criteria: Known central nervous system involvement or brain metastases. New York Heart Association Class III or IV cardiac disease or myocardial infarction within the past 12 months. Known, clinically significant carotid artery disease. Known, increased risk of bleeding. Patients with TE event occurring > 6months prior to enrollment and receiving active anticoagulation. Patients with any prior history of arterial thrombosis or symptomatic pulmonary embolism. Patients with current use of megestrol acetate (use with 10 days of Day 1) will be excluded. Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy. Known active infection with human immunodeficiency virus, hepatitis B, or hepatitis C. Known allergy to hyaluronidase. Patients with prosthetic heart valves Women currently pregnant or breastfeeding. Intolerance of dexamethasone. History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer or curatively-treated cervical carcinoma in-situ. History of transient ischemic attack (TIA) or cerebrovascular accident (CVA). Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications. Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for the study. Inability to comply with study and follow-up procedures as judged by the Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth Yu, MD, MSc
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hartford Healthcare Cancer Institute @ Hartford Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
Miami Cancer Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Memorial Sloan Kettering Basking Ridge
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Facility Name
Lehigh Valley Health Network
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

Study Of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma

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