A Phase II Study of Gemcitabine, Oxaliplatin and Bevacizumab Followed by 5-Fluorouracil, Oxaliplatin, Bevacizumab and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
18 Years
N/A
Both
Pancreatic Cancer
Trial Information
A Phase II Study of Gemcitabine, Oxaliplatin and Bevacizumab Followed by 5-Fluorouracil, Oxaliplatin, Bevacizumab and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate after 6 and 12 weeks of pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
Safety Issue:
No
Principal Investigator
Amy Kramer, RN, MPA
Investigator Affiliation:
Abramson Cancer Center of the University of Pennsylvania
Authority:
Unspecified
Study ID:
CDR0000580812
NCT ID:
NCT00602602
Start Date:
March 2007
Completion Date:
Related Keywords:
- Pancreatic Cancer
- stage IV pancreatic cancer
- recurrent pancreatic cancer
- Pancreatic Neoplasms
Name | Location |
|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
