Chemotherapy With or Without Dalteparin in Treating Patients With Metastatic Pancreatic Cancer (PAM07)

Chemotherapy With or Without Preventive Anticoagulation for Metastatic Cancer of the Pancreas

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, 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 chemotherapy. It is not yet known whether gemcitabine is more effective when given alone or together with dalteparin and/or capecitabine in treating patients with pancreatic cancer.

PURPOSE: This randomized phase III trial is studying whether dalteparin prevents blood clots in patients with pancreatic cancer receiving treatment with different combinations of gemcitabine and capecitabine.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer; Thromboembolism; Chemotherapeutic Agent Toxicity
• Intervention / Treatment: Drug: Chemotherapy at the investigator's discretion; Drug: daltéparine

Detailed Description

OBJECTIVES:

Primary

• To demonstrate that preventive anticoagulation with dalteparin reduces the number of thromboembolic events.
• To determine the number of thromboembolic events occurring with preventive anticoagulation.

Secondary

• To determine survival without thrombotic event.
• To determine progression-free and overall survival.
• To determine time to response of tumor.
• To assess tolerance of these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 4 treatment arms.

• Arm A: Patients receive chemotherapy at investigator's discretion
• Arm B Patients receive chemotherapy at investigator's discretion and dalteparin In all arms, treatment repeats in the absence of disease progression or unacceptable toxicity.

Blood and plasma samples are obtained at baseline and periodically during study. Blood is examined for biomarkers, resistance to activated protein C, and mutations (Leiden V factor, mutation G20210A, and the factor II gene). Thrombin generation and factors VIIa and VIII are assessed in plasma.

After completion of study therapy, patients are followed periodically.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Meaux, France, 77104
    • Centre Hospitalier de Meaux
  • Montfermeil, France, 93370
    • Centre Hospitalier Intercommunal Le Raincy - Montfermeil
  • Paris, France, 75018
    • Hôpital Bichat - Claude Bernard
  • Paris, France, 75651
    • CHU Pitié-Salpêtrière
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Suresnes, France, 92151
    • Hopital Foch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the pancreas

  • Metastatic disease
  • Not amenable to treatment
  • No localized or locally advanced disease
• Measurable disease (metastatic or primary tumor) defined as ≥ 2 cm by CT scan or ≥ 1 cm by spiral CT scan or MRI
• No progressive thrombo-embolic disease
• No adenocarcinoma of the biliary tract or ampulla of Vater
• No known CNS metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy > 12 weeks
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• Alkaline phosphatase < 5 times normal
• Bilirubin < 1.5 times normal
• Creatinine < 1.5 times normal
• Creatinine clearance < 30 mL/min
• Pain controlled or stabilized via analgesic therapy
• Affiliation with social security system
• Not pregnant or nursing
• No controlled or uncontrolled jaundice
• No contraindication to study drugs
• No cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months
• No serious cardiac and/or respiratory disease

• No other cancer in the past 5 years except the following cancers, provided they have been completely resected:

  • Skin cancer
  • Localized melanoma
  • Carcinoma in situ of the cervix
• No history of thrombophilia
• No history of heparin-induced thrombocytopenia
• No uncontrolled or persistent hypercalcemia
• No psychological, familial, social, and/or geographical condition that precludes participation in the study

PRIOR CONCURRENT THERAPY:

• No prior hematologic therapy for metastatic disease
• No prior abdominal radiotherapy
• No concurrent corticosteroids as anti-emetic therapy
• No other concurrent anticoagulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: chemotherapy; chemotherapy at investigator's discretion	Drug: Chemotherapy at the investigator's discretion
Experimental: dalteparin; dalteparin: 5000 UI sub-cutaneous injection, from Day 1 to Day 28.	Drug: Chemotherapy at the investigator's discretion; Drug: daltéparine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboembolic events	number of thromboembolic events during anticoagulation treatment	during study treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	at one year
Progression-free survival	at 6 months
Tolerance of regimens	each cycle

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Investigators: Principal Investigator: Benoist Chibauldel, MD, Hopital Saint Antoine

Publications and helpful links

General Publications

• Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 18, 2008
• First Submitted That Met QC Criteria: April 18, 2008
• First Posted (Estimate): April 21, 2008

Study Record Updates

• Last Update Posted (Estimate): March 13, 2013
• Last Update Submitted That Met QC Criteria: March 12, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: thromboembolism; recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer; chemotherapeutic agent toxicity
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Embolism and Thrombosis; Pancreatic Diseases; Pancreatic Neoplasms; Thromboembolism
• Other Study ID Numbers: CDR0000593019; GERCOR-PAM07-D07-2; EUDRACT 2007-002115-59; EU-20837; PFIZER-GERCOR-PAM07-D07-2