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

August 9, 2013 updated by: Hull University Teaching Hospitals NHS Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

120

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Incidence of venous thromboembolism reduction

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hull University Teaching Hospitals NHS Trust

Investigators

Study Chair: Anthony Maraveyas, Hull University Teaching Hospitals NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2003

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

April 18, 2007

First Submitted That Met QC Criteria

April 18, 2007

First Posted (Estimate)

April 19, 2007

Study Record Updates

Last Update Posted (Estimate)

August 12, 2013

Last Update Submitted That Met QC Criteria

August 9, 2013

Last Verified

April 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

PRH-HCTU-FRAGEM
CDR0000540180 (Registry Identifier: PDQ (Physician Data Query))
PRH-HCTU-FRAGEM-V-12.1
CTA-MF8000/13558
EU-20721
LILLY-PRH-HCTU-FRAGEM
ISRCTN76464767

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