Gemcitabine With or Without Dalteparin in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer - Full Text View

Sponsored by:	Hull and East Yorkshire Hospitals NHS Trust
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00462852

Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with gemcitabine for pancreatic cancer.

PURPOSE: This randomized phase II trial is studying how well gemcitabine works with or without dalteparin in treating patients with locally advanced or metastatic pancreatic cancer.

Condition	Intervention	Phase
Cancer-Related Problem/Condition Pancreatic Cancer	Drug: dalteparin Drug: gemcitabine hydrochloride Procedure: laboratory biomarker analysis	Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine hydrochloride Gemcitabine Pancrelipase Ultrase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Phase II Randomized Study of Chemo-Anticoagulation (Gemcitabine-Dalteparin) Versus Chemotherapy Alone (Gemcitabine) for Locally Advanced and Metastatic Pancreatic Adenocarcinoma [FRAGEM]

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Incidence of venous thromboembolism reduction [ Designated as safety issue: No ]

Secondary Outcome Measures:

Early survival benefit [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Time to disease progression [ Designated as safety issue: No ]
Effect of drug combination on serological markers of thromboangiogenesis [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	April 2003

Detailed Description:

OBJECTIVES:

Primary

Compare the incidence of venous thromboembolism in patients with locally advanced or metastatic pancreatic cancer treated with gemcitabine hydrochloride and dalteparin versus gemcitabine hydrochloride alone.

Secondary

Compare the survival benefit, in terms of increased (from 70% to 85%) survival at 12 weeks, of patients treated with these regimens.
Compare the toxicity of these regimens.
Compare the overall survival of patients treated with these regimens.
Compare the time to disease progression in patients treated with these regimens.
Determine the effect of gemcitabine hydrochloride and dalteparin on serological markers of thromboangiogenesis.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to disease progression (locally advanced vs metastatic) and Karnofsky performance status (≥ 80% vs < 80%). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes once weekly in weeks 1-7 and 9-11.
Arm II: Patients receive low molecular weight dalteparin subcutaneously once daily in weeks 1-12. Patients also receive gemcitabine hydrochloride as in arm I.

Blood samples are acquired at baseline for analysis of circulating tissue factor and vascular endothelial growth factor.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreas
- Patients with clinical 'high probability' of pancreatic cancer and biopsy suggestive but not diagnostic of pancreatic cancer may be eligible based on review by the principal investigator
Measurable or evaluable disease
No clinical evidence of active venous thromboembolism

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 60-100% OR WHO PS 0-2
Life expectancy > 12 weeks
Absolute neutrophil count > 2,000/mm³
WBC > 3,000/mm³
Platelet count > 100,000/mm³
Creatinine clearance > 50 mL/min
INR ≤ 1.5 times upper limit of normal (ULN)
Bilirubin < 1.5 times ULN (stent allowed)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No cerebrovascular accident within the past 6 months
No obvious contraindication to anticoagulation, including the following:
- Bleeding diathesis
- Active peptic ulcer
- Ulcerating cancer into duodenum
No history of other advanced malignancy
No gross hematuria
No melaena or gross evidence of gastrointestinal bleeding (other than piles)
No requirement for a central line
No other significant medial or psychiatric illness that, in the opinion of the investigator, would preclude study participation

PRIOR CONCURRENT THERAPY:

No prior gemcitabine hydrochloride-containing treatment
No other concurrent cytotoxic chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), or experimental medications
No other concurrent specific anticancer therapy as a result of disease progression
No concurrent caval filter device
No other concurrent anticoagulants for venous thromboembolism or other reasons (e.g., atrial fibrillation)
No concurrent acetylsalicylic acid (> 75 mg) as an antiplatelet drug for a preexisting cardiovascular condition
No concurrent clopidogrel bisulfate

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00462852

Locations

United Kingdom, England
Maidstone Hospital	Recruiting
Maidstone, England, United Kingdom, ME16 9QQ
Contact: Justin Waters, MD 44-162-222-5149
Nottingham City Hospital NHS Trust	Recruiting
Nottingham, England, United Kingdom, NG5 1PB
Contact: Sarah Ayres, MD 44-115-969-1169
Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Recruiting
Hull, England, United Kingdom, HU8 9HE
Contact: Anthony Maraveyas 44-148-467-6703
Royal Lancaster Infirmary	Recruiting
Lancaster, England, United Kingdom, LA1 4RP
Contact: David Fyfe, MD 44-152-458-3404
St. George's Hospital	Recruiting
London, England, United Kingdom, SW17 0QT
Contact: Tim Benepal, MD 44-208-725-2995
Scarborough General Hospital	Recruiting
Scarborough, England, United Kingdom, YO12 6QL
Contact: Contact Person 44-0172-334-2175
Scunthorpe General Hospital	Recruiting
Scunthorpe, England, United Kingdom, DN15 7BH
Contact: Contact Person 44-1724-282-282
Saint Bartholomew's Hospital	Recruiting
London, England, United Kingdom, EC1A 7BE
Contact: David Propper, MD 44-207-601-7460 d.j.propper@qmul.ac.uk

Sponsors and Collaborators

Hull and East Yorkshire Hospitals NHS Trust

Investigators

Study Chair:

Anthony Maraveyas

Hull and East Yorkshire Hospitals NHS Trust

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000540180, PRH-HCTU-FRAGEM, PRH-HCTU-FRAGEM-V-12.1, CTA-MF8000/13558, EU-20721, LILLY-PRH-HCTU-FRAGEM, ISRCTN76464767
Study First Received:	April 18, 2007
Last Updated:	October 18, 2008
ClinicalTrials.gov Identifier:	NCT00462852
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

thromboembolism
stage III pancreatic cancer
stage IV pancreatic cancer

adenocarcinoma of the pancreas
recurrent pancreatic cancer
stage II pancreatic cancer

Study placed in the following topic categories:

Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases
Pancrelipase
Thromboembolism
Recurrence
Digestive System Diseases

Dalteparin
Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Adenocarcinoma
Gemcitabine
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Anticoagulants
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Hematologic Agents
Physiological Effects of Drugs
Fibrinolytic Agents

Enzyme Inhibitors
Cardiovascular Agents
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Fibrin Modulating Agents
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009