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

NCT00602602 | Completed Phase 2

• 4 other identifiers: CDR0000580812UPCC-04206GENENTECH-UPCC-04206UPCC-805957
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

stage IV pancreatic cancer; recurrent pancreatic cancer

Outcome Measures

Primary Outcomes (2)

• Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab

  Response rate pre-radiation chemotherapy and bevacizumab and after 5-6 weeks of concurrent chemoradiotherapy and bevacizumab

  after 6-12 weeks

• Progression-free survival

  to be assessed after completion of treatment

  approximately 26 weeks

Secondary Outcomes (1)

• Percentage of potentially resectable patients who are able to proceed to successful resection

  approximately 12 weeks from initial chemo start

Study Arms (1)

GemOx and Bev, then chemoradiation, then surgery

EXPERIMENTAL

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

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

Interventions

bevacizumab BIOLOGICAL

GemOx and Bev, then chemoradiation, then surgery

fluorouracil DRUG

GemOx and Bev, then chemoradiation, then surgery

gemcitabine hydrochloride DRUG

GemOx and Bev, then chemoradiation, then surgery

oxaliplatin DRUG

GemOx and Bev, then chemoradiation, then surgery

immunohistochemistry staining method OTHER

GemOx and Bev, then chemoradiation, then surgery

laboratory biomarker analysis OTHER

GemOx and Bev, then chemoradiation, then surgery

conventional surgery PROCEDURE

GemOx and Bev, then chemoradiation, then surgery

endoscopic biopsy PROCEDURE

GemOx and Bev, then chemoradiation, then surgery

laparoscopy PROCEDURE

GemOx and Bev, then chemoradiation, then surgery

radiation therapy RADIATION

GemOx and Bev, then chemoradiation, then surgery

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Bevacizumab; Fluorouracil; Gemcitabine; Oxaliplatin; Immunohistochemistry; Endoscopic Mucosal Resection; Laparoscopy; Radiotherapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Coordination Complexes; Organic Chemicals; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Therapeutics

Study Officials

• Peter O'Dwyer, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2008
• First Posted: January 28, 2008
• Study Start: March 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: April 27, 2020

Record last verified: 2020-04

Locations

US (1)