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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00462852
• Other study ID #: PRH-HCTU-FRAGEM
• Secondary ID: CDR0000540180PRH
• Status: Completed
• Phase: Phase 2
• First received: April 18, 2007
• Last updated: August 9, 2013
• Start date: April 2003
• Est. completion date: November 2011

Study information

• Verified date: April 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms
• Thromboembolism

Intervention

Drug:
• dalteparin

• gemcitabine hydrochloride

Other:
• diagnostic laboratory biomarker analysis

Locations

Country	Name	City	State
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	Royal Lancaster Infirmary	Lancaster	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Scarborough General Hospital	Scarborough	England
United Kingdom	Scunthorpe General Hospital	Scunthorpe	England

Sponsors (1)

Lead Sponsor	Collaborator
Hull and East Yorkshire Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of venous thromboembolism reduction			No
Secondary	Early survival benefit			No
Secondary	Toxicity			Yes
Secondary	Overall survival			No
Secondary	Time to disease progression			No
Secondary	Effect of drug combination on serological markers of thromboangiogenesis			No