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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00462852
First received: April 18, 2007
Last updated: August 9, 2013
Last verified: April 2007
  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
Pancreatic Cancer
Thromboembolism
Drug: dalteparin
Drug: gemcitabine hydrochloride
Other: diagnostic laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: 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]

Resource links provided by NLM:


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
Study Completion Date: November 2011
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00462852     History of Changes
Other Study ID Numbers: PRH-HCTU-FRAGEM, CDR0000540180, PRH-HCTU-FRAGEM-V-12.1, CTA-MF8000/13558, EU-20721, LILLY-PRH-HCTU-FRAGEM, ISRCTN76464767
Study First Received: April 18, 2007
Last Updated: August 9, 2013
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

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Thromboembolism
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Dalteparin
Heparin, Low-Molecular-Weight
Gemcitabine
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 29, 2014