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

Condition(s) targeted: Pancreatic Cancer; Thromboembolism

Intervention: dalteparin (Drug); gemcitabine hydrochloride (Drug); diagnostic laboratory biomarker analysis (Other)

Phase: Phase 2

Status: Completed

Sponsored by: Hull and East Yorkshire Hospitals NHS Trust

Official(s) and/or principal investigator(s):
Anthony Maraveyas, Study Chair, Affiliation: Hull and East Yorkshire Hospitals NHS Trust

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.

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 design: Allocation: Randomized, Primary Purpose: Treatment

Primary outcome: Incidence of venous thromboembolism reduction

Secondary outcome:

Early survival benefit

Toxicity

Overall survival

Time to disease progression

Effect of drug combination on serological markers of thromboangiogenesis

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Princess Royal Hospital at Hull and East Yorkshire NHS Trust, Hull, England HU8 9HE, United Kingdom

Royal Lancaster Infirmary, Lancaster, England LA1 4RP, United Kingdom

Saint Bartholomew's Hospital, London, England EC1A 7BE, United Kingdom

St. George's Hospital, London, England SW17 0QT, United Kingdom

Maidstone Hospital, Maidstone, England ME16 9QQ, United Kingdom

Nottingham City Hospital, Nottingham, England NG5 1PB, United Kingdom

Scarborough General Hospital, Scarborough, England YO12 6QL, United Kingdom

Scunthorpe General Hospital, Scunthorpe, England DN15 7BH, United Kingdom

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: April 2003
Last updated: August 9, 2013