Gemcitabine, Bevacizumab, and Abdominal Radiation Therapy in Treating Patients With Localized Pancreatic Cancer

NCT00460174 | Completed Phase 2 DMC

• 3 other identifiers: NU 04I6NU-04I6STU00006774
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Bevacizumab may also stop the tumor growth by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Gemcitabine and bevacizumab may make tumor cells more sensitive to radiation therapy. Giving gemcitabine together with bevacizumab and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with bevacizumab and abdominal radiation therapy works in treating patients with localized pancreatic cancer.

Conditions

Pancreatic Cancer

Keywords

stage I pancreatic cancer; stage II pancreatic cancer; stage III pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Response rate

  Response will be measured by CT scans using Recist and defined as Complete Response, Partial Response, Stable disease/no response, Progressive Disease.

  After 10 weeks of concurrent therapy

Secondary Outcomes (1)

• Toxicity profile of bevacizumab and gemcitabine with radiation therapy

  After every cycle of therapy (cycle = 3-4 weeks), then every 3 months for 2 years, then every 6 months for 3 years, then yearly up to 10 years or until disease progression.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Concurrent gemcitabine, bevacizumab, and radiation therapy

Biological: bevacizumab; Drug: gemcitabine; Procedure: conventional surgery; Radiation: radiation therapy

Interventions

bevacizumab BIOLOGICAL

10 mg/kg every 2 weeks as an intravenous infusion after gemcitabine and before radiation

Also known as: Avastin

Treatment Arm

gemcitabine DRUG

1000 mg/m2, 30 minute intravenous infusion, cycle 1 (weeks 1, 2), cycle 2 (weeks 4, 5, 6) and cycle 3 (weeks 8 and 9). During cycle 2, gemcitabine will be delivered prior to radiation therapy

Also known as: gemcitabine hydrochloride

Treatment Arm

conventional surgery PROCEDURE

If resectable, patients will undergo surgery no less than 6 weeks following last dose of bevacizumab. Unresectable patients will not undergo surgery.

Treatment Arm

radiation therapy RADIATION

2.4 Gy fractions, 5 fractions/week during cycle 2 only (weeks 4, 5, 6). Total dose 36 Gy.

Treatment Arm

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of localized pancreatic cancer * No metastatic disease * Resectable or unresectable tumor based on spiral CT with both oral and intravenous contrast enhancement, defined by the following National Comprehensive Cancer Network (NCCN) criteria for resectability\*: * Resectable tumors meeting the following criteria: * No distant metastases * Clear fat plane around celiac and superior mesenteric arteries * Patent superior mesenteric vein/portal vein * Tumors considered borderline resectable according to NCCN criteria, including any of the following, are considered unresectable for the purpose of this study: * Severe unilateral superior mesenteric vein/portal impingement * Tumor abutment on the superior mesenteric artery * Gastroduodenal artery encasement up to the origin at the hepatic artery * Colon invasion NOTE: \*Determination of resectability must be made prior to study entry based on NCCN criteria * Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiotherapy * Radiographically assessable disease * Malignant disease must be encompassable within a single irradiation field * No gross duodenal invasion noted on endoscopy * No CNS or brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for up to 3 months after completion of study therapy * Bilirubin ≤ 2.0 mg/dL * AST or ALT ≤ 2.5 times upper limit of normal * Urine protein:creatinine ratio \< 1.0 * Proteinuria \< 2+ by dipstick urinalysis OR baseline protein ≤ 1 g/24-hour urine collection * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9.0 g/dL (transfusion or epoetin alfa support allowed) * INR ≤ 1.5 * No other malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix, uterus, or bladder * No concurrent significant infection or other medical condition that would preclude protocol treatment * No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would contraindicate use of an investigational drug, affect the interpretation of the results of the study, or render the patient at high risk for treatment complications * No clinically significant cardiac disease, including any of the following: * Uncontrolled hypertension (i.e., blood pressure \> 150/100 mm Hg despite antihypertensive medication) * Myocardial infarction within the past year * Unstable angina * New York Heart Association class II-IV congestive heart failure * Unstable symptomatic arrhythmia requiring medication * Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed * No clinically significant peripheral vascular disease * No evidence of bleeding diathesis or coagulopathy * No significant traumatic injury within the past 28 days * No serious, nonhealing wound or ulcer, or concurrent healing fracture * No history of aneurysm, stroke, transient ischemic attack, or arteriovenous malformation * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior treatment for pancreatic cancer * More than 5 years since prior chemotherapy for malignancies other than pancreatic cancer * No prior radiotherapy to the target volume * More than 28 days since prior major surgical procedure or open biopsy * At least 28 days since prior surgical bypass * More than 7 days since prior fine-needle aspiration or core biopsy * No prior organ transplant * At least 4 weeks since prior sorivudine or brivudine * At least 30 days since prior cimetidine * No concurrent major surgical procedure

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

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Related Publications (2)

• Small W Jr, Mulcahy M, Benson A, et al.: A phase II trial of weekly gemcitabine and bevacizumab in combination with abdominal radiation therapy in patients with localized pancreatic cancer. [Abstract] J Clin Oncol 25 (Suppl 18): A-15043, 637s, 2007.

  RESULT

• Rezai P, Yaghmai V, Tochetto SM, Galizia MS, Miller FH, Mulcahy MF, Small W Jr. Change in the growth rate of localized pancreatic adenocarcinoma in response to gemcitabine, bevacizumab, and radiation therapy on MDCT. Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):452-9. doi: 10.1016/j.ijrobp.2010.05.060. Epub 2011 May 11.

  PMID: 21570199 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Bevacizumab; Gemcitabine; 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; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics

Study Officials

• William Small, MD

  Robert H. Lurie Cancer Center

  STUDY CHAIR

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: April 11, 2007
• First Posted: April 13, 2007
• Study Start: October 10, 2005
• Primary Completion: December 17, 2007
• Study Completion: July 16, 2010
• Last Updated: October 29, 2018

Record last verified: 2018-10

Locations

US (1)