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

Phase 2

Completed

• Conditions: Pancreatic Cancer
• Interventions: 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

• Registration Number: NCT00602602
• Lead Sponsor: Abramson Cancer Center at Penn Medicine

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.

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2008-01-22
• Study First Submitted QC: 2008-01-22
• Study First Posted: 2008-01-28
• Primary Completion: 2011-09
• Study Completion: 2011-09
• Status Verified: 2020-04
• Disposition First Submitted: 2020-04-06
• Disposition First Submitted QC: 2020-04-22
• Last Update Submitted: 2020-04-22
• Disposition First Posted: 2020-04-27
• Last Update Posted: 2020-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GemOx and Bev, then chemoradiation, then surgery	gemcitabine hydrochloride	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	immunohistochemistry staining method	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	laboratory biomarker analysis	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	oxaliplatin	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	endoscopic biopsy	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	bevacizumab	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	radiation therapy	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	conventional surgery	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	laparoscopy	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention
GemOx and Bev, then chemoradiation, then surgery	fluorouracil	Gemcitabine 1000 mg/m2 over 100 min on day 1 every 2 weeks Oxaliplatin 85 mg/m2 over 2 hours on day 2 every 2 weeks Bevacizumab 10 mg/kg over 90 minutes on day 1 every 2 weeks. Infusion duration may be shortened in subsequent courses if tolerated. One cycle is 2 weeks. Chemoradiation to begin prior to 4 weeks from last dose of Gem. Between 4 and 6 weeks following chemoradiotherapy, patients will undergo re-staging with CT or MRI and CA 19-9. If there is no evidence of disease progression, the patient will be referred to the surgeon for re-evaluation and consideration of surgical intervention

Primary Outcome Measures

Name	Time	Method
Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab	after 6-12 weeks	Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab
Progression-free survival	approximately 26 weeks	to be assessed after completion of treatment

Secondary Outcome Measures

Name	Time	Method
Percentage of potentially resectable patients who are able to proceed to successful resection	approximately 12 weeks from initial chemo start	after chemoradiation, those who can proceed to surgery

Trial Locations

Locations (1)

Abramson Cancer Center of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States