Gemcitabine With or Without Dalteparin in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

Sponsor

Hull University Teaching Hospitals NHS Trust (Other)

Overall Status

Completed

CT.gov ID

NCT00462852

Collaborator

(none)

120

Enrollment

Locations

103

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Pancreatic Cancer Thromboembolism	Drug: dalteparin Drug: gemcitabine hydrochloride Other: diagnostic laboratory biomarker analysis	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase II Randomized Study of Chemo-Anticoagulation (Gemcitabine-Dalteparin) Versus Chemotherapy Alone (Gemcitabine) for Locally Advanced and Metastatic Pancreatic Adenocarcinoma [FRAGEM]

Study Start Date :

Apr 1, 2003

Actual Study Completion Date :

Nov 1, 2011

Outcome Measures

Primary Outcome Measures

Incidence of venous thromboembolism reduction []

Secondary Outcome Measures

Early survival benefit []
Toxicity []
Overall survival []
Time to disease progression []
Effect of drug combination on serological markers of thromboangiogenesis []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England	United Kingdom	HU8 9HE
2	Royal Lancaster Infirmary	Lancaster	England	United Kingdom	LA1 4RP
3	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
4	St. George's Hospital	London	England	United Kingdom	SW17 0QT
5	Maidstone Hospital	Maidstone	England	United Kingdom	ME16 9QQ
6	Nottingham City Hospital	Nottingham	England	United Kingdom	NG5 1PB
7	Scarborough General Hospital	Scarborough	England	United Kingdom	YO12 6QL
8	Scunthorpe General Hospital	Scunthorpe	England	United Kingdom	DN15 7BH