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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00602602
First received: January 22, 2008
Last updated: July 7, 2009
Last verified: July 2009
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab [ Designated as safety issue: No ]
  • Time to progression after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of potentially resectable patients who are able to proceed to successful resection [ Designated as safety issue: No ]

Estimated Enrollment: 99
Study Start Date: March 2007
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Second

  • 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.

OUTLINE:

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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)

PRIOR CONCURRENT THERAPY:

  • 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
  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: NCT00602602

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Clinical Trials Office - Abramson Cancer Center of the Univers    800-474-9892      
Sponsors and Collaborators
University of Pennsylvania
Investigators
Investigator: Amy Kramer, RN, MPA Abramson Cancer Center of the University of Pennsylvania
  More Information

Additional Information:
No publications provided

Responsible Party: Amy Kramer, Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00602602     History of Changes
Other Study ID Numbers: CDR0000580812, UPCC-04206, GENENTECH-UPCC-04206, UPCC-805957
Study First Received: January 22, 2008
Last Updated: July 7, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV pancreatic cancer
recurrent pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Bevacizumab
Gemcitabine
Oxaliplatin
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014