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Phase II Study of Coagulation Factor VIIa Inhibitor PCI-27483 in Pancreatic Cancer Patients Receiving Treatment With Gemcitabine, Part A

Phase 2
18 Years
Open (Enrolling)
Pancreatic Cancer, Ductal Adrenocarcinoma, Exocrine Pancreatic Cancer

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Trial Information

Phase II Study of Coagulation Factor VIIa Inhibitor PCI-27483 in Pancreatic Cancer Patients Receiving Treatment With Gemcitabine, Part A

This study will be conducted in three segments: Part A, Part B and Part C. Parts A and B
are 12 weeks of treatment followed by 4 weeks of evaluation. In part A patients will
dose-escalate up to three dose levels of PCI-27483 administered as subcutaneous (SC)
injections twice-daily (BID). Part B to start once 4th patient completes 90 of 112 doses in
8 weeks. In part B patients are randomized to PCI-27483 and gemcitabine (active arm) OR
gemcitabine only (control arm). PCI-27483 doses in both Part A and B will be administered in
combination with a standard regimen of gemcitabine. Patients with a tumor response or stable
disease at 12 weeks will have the opportunity to continue PCI-27483 treatment until disease
progression or the Investigator considers the study treatment to be no longer tolerable.
Treatment with gemcitabine in either the active or control arm may continue until a standard
course of gemcitabine therapy has been completed. Patients will complete Part A or Part B
after 16 weeks on study regardless of treatment duration. Evaluable patients will roll over
into part C and be followed for 12 months from enrollment (first dose).

Inclusion Criteria:

1. Men or women at least 18 years old

2. Body weight ≥ 40 and ≤ 100 kg.

3. Part A: Metastatic ductal adenocarcinoma of the pancreas diagnosed ≤ 4 months prior
to enrollment. (Locally advanced does not have any criteria)

4. Part B: Locally advanced ductal adenocarcinoma of the pancreas diagnosed ≤ 3 months
prior to enrollment or metastatic ductal adenocarcinoma diagnosed ≤ 2 months.

5. Measurable disease by spiral CT scan (SCT) in accordance with RECIST criteria.

6. Patients after non-curative surgery are eligible if at least 4 weeks after surgery
and recovered from significant surgical morbidity.

7. Estimated life expectancy of at least 4 months.

8. ECOG performance status 0 to 1.

9. Normal baseline coagulation function as defined by:

1. PT 10-16 seconds, and

2. aPTT 22-38 seconds.

10. Agree to not participate in contact sports or strenuous activity while taking

11. Ability to understand the study, willingness to participate in the study for the
study duration, and ability to provide written informed consent to participate.

Exclusion Criteria:

1. History of any clinically significant medical condition that, in the opinion of the
Principal Investigator, would interfere with the study evaluation or interpretation.

2. Known history of brain metastases.

3. Any evidence of intra-cranial hemorrhage based on head CT scan within 30 days of

4. History of disease progression while being treated with gemcitabine.

5. Radiotherapy of the primary tumor or unwillingness to defer radiotherapy of the
primary tumor until > 3 months from initiation of treatment.

6. History of venous thromboembolism (eg, deep vein thrombosis, pulmonary embolism,and
arterial thromboembolism) or other indications for anticoagulant treatment
(eg,mechanical heart values, atrial fibrillation, etc.) within the last year. Local
thrombus in the mesenteric or portal vein is acceptable.

7. Uncontrolled hypertension (systolic > 160 or diastolic > 100 mm Hg on medical

8. Continued anticoagulation therapy or anticoagulation therapy within 2 months prior to
enrollment, except for perisurgical prophylaxis which must have ceased 2 weeks before

9. Contraindication to systemic anticoagulation.

10. Continued treatment with antiplatelet drugs including aspirin, clopidogrel, etc.
within the past 72 hours.

11. Known history of clinically significant or recurrent bleeding episodes, including
significant bleeding after surgery, childbirth, or dental extraction.

12. Patients with documented invasion of adjacent organs by CT scan (e.g. stomach,
duodenum) are not eligible

13. Patients known to have esophageal varicose are not eligible

14. Known history of a congenital coagulation factor deficiency.

15. Known acquired or hereditary platelet disorder.

16. Known history of immunodeficiency.

17. Women of child-bearing potential or sexually active men, unwilling to use adequate
contraceptive protection during the course of the study.

18. Pregnant or lactating women (female patients of childbearing potential must have a
negative serum pregnancy test within 14 days of first day of drug dosing, or if
positive, pregnancy ruled out by ultrasound).

19. Laboratory Abnormalities:

1. Serum creatinine > 2 mg/dL or creatinine clearance < 50 mL/minute (using
Cockroft Gault formula)

2. AST and ALT ≥ 4.0 x upper limit of normal (ULN).

3. Bilirubin ≥ 3 mg/dL.

4. Alkaline phosphatase > 5 x ULN.

5. Albumin < 2.0g/dL.

6. Hemoglobin < 9.0 g/dL.

7. Platelet count < 100,000/μL.

20. Evidence of active gastrointestinal tract bleeding, including guaiac stool
positivity,excluding hemorrhoidal bleeding

21. Chronic active hepatitis B or C.

22. Known HIV infection.

23. Participation in any study of an investigational device, medication, biologic, or
other agent within 30 days prior to enrollment, or planned participation within the
study duration.

24. Risk factors for, or use of medications known to prolong QTc interval or that may be
associate with Torsades de Pointes within 7 days of treatment start (see Appendix J.
Risk Factors for Drug-induced Torsades de Pointes).

25. QTc prolongation (defined as a QTc ≥ 450 msec) or other significant ECG abnormalities
including 2nd degree AV block type II, 3rd degree AV block, or bradycardia
(ventricular rate less than 50 beats/min). If 2 screening ECGs have a QTc ≥ 450 msec,
the ECGs can be submitted for a centralized, cardiologic evaluation and if determined
to be < 450 msec then the patient is eligible.

Type of Study:


Study Design:

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

Outcome Measure:

Adverse event profile (In Part A, dose levels will be compared to each other and in Part B the PCI-27483 arm will be compared to the control arm), from the time of the first dose till 28 days after the last dose of study treatment

Outcome Time Frame:

First dose till 28 days after last dose of PCI-27483 or gemcitabine whichever occurs last.

Safety Issue:


Principal Investigator

Eric Hedrick, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

November 2009

Completion Date:

December 2012

Related Keywords:

  • Pancreatic Cancer
  • Ductal Adrenocarcinoma
  • Exocrine Pancreatic Cancer
  • PCI-27483
  • Factor VIIa
  • Gemcitabine
  • 4 months life expectancy
  • Pharmacyclics
  • Locally Advanced
  • Metastatic disease
  • Pancreatic Neoplasms



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Columbia UniversityNew York, New York  10032-3784
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TGen Clinical Reserch Services at Scottsdale HealthcareScottsdale, Arizona  85258
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South Carolina Cancer Specialists, PAHilton Head, South Carolina  29926
University of Vermont/Vermont Cancer CenterBurlington, Vermont  05401