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Bevacizumab, Combination Chemotherapy, and Radiation Therapy in Treating Patients Undergoing Surgery For Locally Advanced Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00602602
Recruitment Status : Active, not recruiting
First Posted : January 28, 2008
Last Update Posted : August 29, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Brief Summary:

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with combination chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: The phase II trial is studying the side effects and how well giving bevacizumab together with gemcitabine, oxaliplatin, fluorouracil, and radiation therapy works in treating patients undergoing surgery for locally advanced pancreatic cancer.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Biological: bevacizumab Drug: fluorouracil Drug: gemcitabine hydrochloride Drug: oxaliplatin Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: conventional surgery Procedure: endoscopic biopsy Procedure: laparoscopy Radiation: radiation therapy Phase 2

Detailed Description:



  • To describe the toxicity of bevacizumab with gemcitabine and oxaliplatin, when therapy is given before chemoradiotherapy, in patients with locally advanced pancreatic cancer.
  • To describe the toxicity of bevacizumab with oxaliplatin, fluorouracil, and concomitant radiotherapy in these patients.
  • To define progression-free survival, time to progression, and overall survival of patients treated with this regimen.


  • To determine the percentage of potentially resectable patients who are ultimately able to proceed to successful resection.
  • To determine the relationship between markers of apoptosis in tumor cells (including MIF, CREB, HIF-1-alpha expression/polymorphism, and others) and response to therapy.
  • To define response rates in patients treated with this regimen.


  • Neoadjuvant therapy: Patients receive gemcitabine IV over 100 minutes and bevacizumab IV over 30-90 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Between 4-6 weeks after completion of initial therapy, patients undergo radiotherapy once daily, 5 days a week, for 5-6 weeks. Beginning within 48 hours after initiation of radiotherapy, patients receive fluorouracil IV continuously through completion of radiotherapy. Patients also receive concurrent oxaliplatin IV over 2 hours on days 1, 15 and 29 and bevacizumab IV on days 1 and 15.
  • Surgery: Four to six weeks after completion of neoadjuvant therapy, patients undergo resection of the tumor. Patients with no evidence of disease progression and who undergo successful surgical intervention (i.e., R0 resection) proceed to adjuvant chemotherapy within the next 6-10 weeks.
  • Adjuvant therapy: Patients receive gemcitabine and bevacizumab for 4 courses as in neoadjuvant therapy.

Patients undergo collection of tumor tissue samples at the time of diagnosis, prior to treatment by endoscopic ultrasound or laparoscopy, or during surgical resection following neoadjuvant therapy. Paraffin-embedded tumor tissue specimens obtained at baseline are analyzed by immunohistochemistry to assess tumor vascularity and angiogenic activity. Tumor vascularity is assessed via immunostaining of tumor specimens with the pan-endothelial cell marker, anti-CD34, for evaluation of tumor blood vessels. Angiogenic activity is assessed by analyzing pERK1/2, Ki67, and the pericyte coverage index in tumor specimens. Patients also undergo blood collection to determine plasma levels of VEGF at 4 weeks prior to initial chemotherapy and bevacizumab, at up to 48 hours prior to chemoradiotherapy and bevacizumab, and at up to 48 hours prior to adjuvant chemotherapy and bevacizumab.

After completion of study therapy, patients are followed every 2 months for the first year, and then every 3 months thereafter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Gemcitabine, Oxaliplatin and Bevacizumab Followed by 5-Fluorouracil, Oxaliplatin, Bevacizumab and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
Study Start Date : March 2007
Actual Primary Completion Date : December 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Primary Outcome Measures :
  1. Response rate after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
  2. Time to progression after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
  3. Progression-free survival
  4. Overall survival

Secondary Outcome Measures :
  1. Percentage of potentially resectable patients who are able to proceed to successful resection

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed adenocarcinoma of the pancreas

    • Resectable, marginally resectable, or unresectable disease determined by one of the following:

      • Contrast-enhanced helical-CT scan
      • Endoscopic ultrasound with biopsy (in patients who do not have metastatic or grossly unresectable disease)
      • Dedicated pancreatic MRI
    • Tumor must be locally advanced or potentially resectable, as determined by one of the following:

      • Abutment of the portal or superior mesenteric veins, hepatic or superior mesenteric artery
      • Extension to the origin of gastroduodenal artery
      • Occlusion of the superior mesenteric vein for < 2 cm
  • Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT

    • Marker elevation alone not allowed as justification for study entry
  • Formalin-fixed, paraffin-embedded tumor tissue specimens from prior biopsy or surgical resection allowed for correlative studies
  • No known brain metastases or tumor metastatic to the peritoneum, liver, or other organs


  • ECOG performance status 0-1
  • ANC ≥1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine < 1.5 times ULN
  • Bilirubin < 2.0 mg/dL (≤ 10 mg/dL for patients with biliary obstruction by tumor)

    • A biliary stent ≥ 9F or biliary bypass is required before treatment if there is biliary obstruction by tumor
  • Urine protein:creatinine ratio ≤ 1.0
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No significant traumatic injury within the past 28 days
  • No serious non-healing wounds, ulcers, or bone fractures
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No myocardial infarction, unstable angina, or cerebrovascular accident within the past 6 months
  • No NYHA class II-IV congestive heart failure

    • Class II defined as symptoms of fatigue, dyspnea or other symptoms with ordinary physical activity
  • No clinically significant peripheral vascular disease
  • Pre-existing hypertension allowed, provided that the patient is receiving a stable antihypertensive regimen and has a blood pressure ≤ 150/100 mm Hg at the time of enrollment
  • Must have adequate oral intake of > 1500 calories/day and be able to maintain hydration OR have access for supplemental enteral feeding (nasoenteral tube, feeding jejunostomy, or percutaneous endoscopic gastrostomy tube)


  • No prior chemotherapy or radiotherapy for pancreatic cancer
  • More than 28 days since prior and no anticipated need for concurrent major surgical procedures
  • More than 7 days since prior minor surgical procedures such as laparoscopy, fine needle aspirations, or core biopsies
  • No treatment plan requiring treatment of > 50% of the liver at a dose > 30 Gy or > 50% of the total kidney volume at a dose > 18 Gy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No oral or parenteral anticoagulation unless patients is receiving a stable dose of anticoagulant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00602602

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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
National Cancer Institute (NCI)
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Principal Investigator: Peter O'Dwyer, MD Abramson Cancer Center of the University of Pennsylvania

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Responsible Party: Abramson Cancer Center of the University of Pennsylvania Identifier: NCT00602602     History of Changes
Other Study ID Numbers: CDR0000580812
First Posted: January 28, 2008    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
stage IV pancreatic cancer
recurrent pancreatic cancer
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors