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A Randomized Phase II Open Label Study to Assess the Efficacy & Safety of Gemcitabine + Abraxane® With or Without ODSH (2-0, 3-0 Desulfated Heparin) as First Line Treatment of Metastatic Pancreatic Cancer

Phase 2
18 Years
75 Years
Open (Enrolling)
Metastatic Pancreatic Cancer

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Trial Information

A Randomized Phase II Open Label Study to Assess the Efficacy & Safety of Gemcitabine + Abraxane® With or Without ODSH (2-0, 3-0 Desulfated Heparin) as First Line Treatment of Metastatic Pancreatic Cancer

ODSH has demonstrated in vitro and in vivo inhibitory activity on mechanisms that are
believed to play important roles in pancreatic cancer invasion, metastasis, and resistance
to chemotherapy and radiation. Pancreatic cancer appears to have a dependence on autophagy,
a regulated catabolic pathway to degrade and recycle cellular organelles and macromolecules.
Autophagy appears to be largely driven by the binding of high mobility group box-1 protein
(HMGB1) to the receptor for advanced glycation end-products (RAGE), which is strongly
inhibited by ODSH. Autophagy appears to not only assist pancreatic cancer cells to survive
in a hypoxic, relatively avascular environment, but also appears to play an important role
in chemotherapy resistance. Other important biological activities promoting pancreatic
cancer invasion and metastasis affected by ODSH include the inhibition of heparanase and the
binding of tumor cells to endothelium and platelets mediated by the selectins. It is
believed that these biological activities such as the inhibition of RAGE, heparanase, and
selectin-mediated metastasis, can be inhibited by ODSH at dose levels that can safely be
administered without clinically significant anticoagulation.

The standard of care of pancreatic cancer is evolving. It appears that two combination
regimens, the "FOLFIRINOX" regimen (a combination of 5-fluorouracil, leucovorin, irinotecan
and oxaliplatin) and the combination of gemcitabine + nab-paclitaxel, could have more
activity than the previous standard treatment of gemcitabine alone.

Subjects with advanced metastatic pancreatic cancer that have not received chemotherapy,
surgical or radiation treatments and have a good performance status will be eligible to
participate in this study. 10 patients will be enrolled in a Run-in Period to receive
gemcitabine + nab-paclitaxel +ODSH. PK sampling and safety assessments will be conducted to
decide on the continuation to the Controlled Period of the study where 50 patients will be
randomized at a 1:1 ratio to either of the two study arms: Arm A will receive gemcitabine +
nab-paclitaxel + ODSH and Arm B will receive gemcitabine + nab-paclitaxel.

The primary endpoint of the study is mean progression free survival. The secondary
endpoints consist of tumor response by RECIST criteria, overall survival at the end of the
study and changes from baseline for CA19-9 marker, weight and plasma albumin.

Inclusion Criteria:

1. Patients must have histologically confirmed adenocarcinoma of the pancreas that is
metastatic and for which potential curative measures, such as resection of an
isolated metastasis, are not available. Patients with islet cell neoplasms are

2. Patient has one or more metastatic tumors measurable by CT scan AND a serum CA19-9
measurement > 2 times the upper limit of normal. Patients must have measurable
disease, defined as at least one lesion that can be accurately measured in at least
one dimension (longest diameter to be recorded for non-nodal lesions and short axis
for nodal lesions) as >20 mm with conventional techniques or as >10 mm with spiral CT

3. Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 75 years of age. If a
female patient is of child-bearing potential, she must have a negative serum
pregnancy test documented within 72 hours prior to the first administration of study
drug and on Day 1 of each cycle thereafter. If sexually active, the patient must
agree to use contraception prior to study entry and for the duration of study

4. Patients must have received no prior radiotherapy or chemotherapy for metastatic
disease. Patients who have received radiotherapy or chemotherapy as adjuvant o
neo-adjuvant therapy for locally advanced disease six months or more prior to
enrollment into this study are eligible.

5. Patient has adequate biological parameters as demonstrated by the following blood
counts at Screening (obtained ≤ 14 days prior to randomization) and at Baseline-Day
0: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count ≥ 100,000/mm3 (100 ×
109/L); Hemoglobin (Hgb) ≥ 9 g/dL.

6. Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days
prior to randomization) and at Baseline-Day 0:

- AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver
metastases are present, then ≤ 5 × ULN is allowed. Total bilirubin ≤ 1.5 × ULN.

- Serum creatinine (Cr) within normal limits or calculated clearance ≥ 60
mL/min/1.73 m2 for patients with creatinine (Cr) levels above or below the
institutional normal value. If using Cr clearance, actual body weight should be
used for calculating Cr clearance (e.g., using the Cockcroft-Gault formula).

7. Patient has acceptable coagulation studies at Screening (obtained ≤14 days prior to
randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin
time (PTT) within normal limits (± 15%).

8. Patient has ECOG performance status ≤ 1.

Exclusion Criteria:

1. Patient has brain metastases.

2. Patient has only locally advanced disease.

3. Patient has experienced an increase of ECOG to > 1 between Screening and

4. Patient requires continuous treatment with coumadin or other oral or parenteral
anticoagulation (heparin, LMWH, heparinoids) to prevent or treat thromboembolic
disease. The use of prophylactic antiplatelet drugs such as clopidogrel and aspirin
are allowed before and during the study.

5. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring
systemic therapy.

6. Patient has undergone major surgery, other than diagnostic surgery (i.e.--surgery
done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks
prior to Randomization in this study.

7. Patient has a history of allergy or hypersensitivity to any of the study drugs, their
pharmaceutical class or any of their excipients.

8. Patient has a concomitant serious medical or psychiatric illness that, in the opinion
of the investigator, could compromise the patient's safety or the study data

9. Patient is enrolled in any other clinical protocol or investigational trial
involving administration of antineoplastic compounds for the treatment of metastatic
pancreatic cancer.

10. Patient is unwilling or unable to comply with study procedures.

11. Nab-paclitaxel is metabolized by CYP2C8 and CYP3A4. Co-administration of substrates,
inhibitors of CYP2C8 and/or CYP3A4 with nab-paclitaxel is not allowed. The following
medications and substances are not allowed during the study: ritonavir, saquinavir,
indinavir, nelfinavir, rifampicin, carbamazepine, phenytoin, efavirenz, or
nevirapine, grapefruit (juice or seeds) or some herbals like St. John's wort.

12. Subjects with risk factors for or a history of Torsades des Pointes (TdP), or a
significant QT prolongation that in the opinion of the investigator may place the
study subject at risk.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-Free Survival (PFS) according to RECIST Guidelines.

Outcome Description:

Median Progression-Free Survival according to RECIST Guidelines Version 4.03

Outcome Time Frame:

From Baseline to disease progression or death (whichever occurs first), assessed up to 9 months.

Safety Issue:


Principal Investigator

Mitesh J Borad, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic , Scottsdale Arizona


United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

March 2013

Related Keywords:

  • Metastatic Pancreatic Cancer
  • Pancreatic Cancer
  • Pancreatic Neoplasms



Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
University of Texas Medical BranchGalveston, Texas  77555-1329
South Texas Oncology & HematologySan Antonio, Texas  78207
Mayo Clinic ArizonaScottsdale, Arizona  85259
Medical University of South Carolina Hollings Cancer CenterCharleston, South Carolina  29425
Saint Mary's Health CareGrand Rapids, Michigan  49503
Cleveland Clinic FloridaWeston, Florida  33331
UPMC Cancer CenterPittsburgh, Pennsylvania  15232
Disney Family Cancer CenterBurbank, California  91505
Marin Cancer CareGreenbrae, California  94904
Scripps Clinic Torrey Pines ( Green Hospital)La Jolla, California  92037
Loyola University Medical Center/Cardinal Bernardin Cancer CenterMaywood, Illinois  60153
Indiana University Health, Goshen Center for Cancer CareGoshen, Indiana  46526
Fesit-Weiller Cancer CenterShreveport, Louisiana  71130
Summa Health System - Cooper Cancer CenterAkron, Ohio  44304
Thomas Jefferson University [Kimmel Cancer Center]Philadelphia, Pennsylvania  19107