Bevacizumab, Erlotinib and Capecitabine for Advanced Pancreatic Cancer

NCT00614653 | Completed Phase 1

• 2 other identifiers: 2007-0044NCI-2010-01549
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of capecitabine, erlotinib hydrochloride, and bevacizumab that can be given in combination with radiation to patients with pancreatic cancer.

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer; Bevacizumab; Avastin™; Anti-VEGF monoclonal antibody; rhuMAb-VEGF; Erlotinib; Erlotinib Hydrochloride; Tarceva; OSI-774; Capecitabine; Xeloda

Outcome Measures

Primary Outcomes (1)

• Highest Tolerated Dose of Capecitabine, Erlotinib Hydrochloride, and Bevacizumab + Radiation

  Any of these events considered a dose-limiting toxicity. 1. Any grade 4 hemorrhage, grade 2 pulmonary or CNS hemorrhage 2. Cardiac arrhythmia 3. Grade 4 congestive heart failure 4. Grade 4 hypertension or reversible posterior leukoencephalopathy syndrome (RPLS) 5. Grade 4 nephrotic syndrome 6. Grade 4 diarrhea 7. Grade 4 rash 8. Pulmonary adverse event related to erlotinib 9. Bowel perforation 10. Symptomatic Grade 4 venous thromboembolic event, or any grade arterial thromboembolic event 11. Wound dehiscence requiring medical or surgical intervention 12. Determination by the investigator that it is no longer safe for the subject to continue therapy

  5 1/2 Weeks

Secondary Outcomes (1)

• Response Rate of Addition of Bevacizumab and Erlotinib to Capecitabine-Based Chemoradiation

  4 to 6 weeks after radiation treatment

Study Arms (1)

Bevacizumab, Erlotinib + Capecitabine

EXPERIMENTAL

Bevacizumab intravenous (IV) every 2 weeks at 5 mg/kg, Erlotinib 100 mg orally (PO) daily + Capecitabine 400 mg/m2 PO twice daily (BID) only on days of radiation. Radiation treatment once daily for 5 1/2 weeks or 28 doses, Dose 50.4 Gy.

Drug: Bevacizumab; Drug: Erlotinib; Drug: Capecitabine; Radiation: Radiation Therapy

Interventions

Bevacizumab DRUG

5 mg/kg IV Over 90 Minutes Every 2 Weeks

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Bevacizumab, Erlotinib + Capecitabine

Erlotinib DRUG

100 mg by mouth Once Daily on days with radiation.

Also known as: OSI-774, Tarceva

Bevacizumab, Erlotinib + Capecitabine

Capecitabine DRUG

400 mg/m\^2 PO Twice Daily on days with radiation.

Also known as: Xeloda

Bevacizumab, Erlotinib + Capecitabine

Radiation Therapy RADIATION

Radiation treatment once daily for 5 1/2 weeks or 28 doses, Dose 50.4 Gy

Also known as: XRT, RT, radiotherapy

Bevacizumab, Erlotinib + Capecitabine

Eligibility Criteria

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

You may qualify if:

• ECOG performance status of 0 or 1.
• Patients must be \>/= 18 years of age. There will be no upper age restriction.
• Cytologic or histologic proof of adenocarcinoma of the pancreas. Patients can have tumor originating in any part of the pancreas. Islet cell tumors are not eligible. Only patients with non- metastatic, unresectable disease are eligible. Patients who cannot undergo resection because of underlying medical problems are also eligible. Patients with regional nodal disease are eligible.
• All patients must be staged with a physical exam, CXR, and contrast-enhanced helical thin-cut abdominal CT. Unresectability is defined by CT criteria: a) evidence of tumor extension to the celiac axis or superior mesenteric (SM) artery, or b) evidence on either CT or angiogram of occlusion of the SM vein or SM/ portal vein confluence. If a tumor does not meet this definition and is found to be unresectable at surgical exploration, then that tumor is considered unresectable.
• Patients may have received prior chemotherapy but not prior radiation therapy to the upper abdomen.
• Bone marrow function: absolute neutrophil count (ANC) \>1,500/ul. Platelets \>100,000/ul.
• Hepatic function: Total bilirubin less than 5mg/dL. If the patient required an endobiliary stent, the bilirubin level must have declined on consecutive measurements indicating adequate biliary decompression; alanine aminotransferase (ALT) \</= 5 times the upper limit of normal.
• Renal function: BUN \</= 30 mg%, creatinine \</= 1.5 mg% and creatinine clearance \>/= 30ml/min (estimated as calculated with Cockcroft-Gault equation). Note: In patients with moderate renal impairment (estimated creatinine clearance 30-50 mL/min) at baseline, a dose reduction to 75% of the capecitabine starting dose is recommended.
• Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary.

You may not qualify if:

• Prior abdominal radiotherapy.
• Imaging (CT or MRI) or endoscopic evidence of direct duodenal invasion by tumor.
• Prior therapy with bevacizumab, cetuximab, or gefitinib. Prior therapy with erlotinib is permitted unless the patient was taken off erlotinib due to treatment failure.
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study.
• Prior severe infusion reaction (bronchospasm, stridor, urticaria and/or hypotension) to a monoclonal antibody.
• Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil.
• Proteinuria at baseline or clinically significant impairment of renal function as demonstrated by urine dipstick for proteinuria \>/= 2+ (patients discovered to have \>/= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \</= 1g of protein in 24 hours to be eligible).
• Prior history of cancer within the last five years except for basal cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with previous malignancies but without evidence of disease for 5 years will be allowed to enter the trial.
• Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Women / men of childbearing potential not using a reliable contraceptive method (oral contraceptive , other hormonal contraceptive, intrauterine device, diaphragm or condom). (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 30 days from the date of the last study drug administration.
• Serious, uncontrolled, concurrent infection(s) requiring IV antibiotics or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
• Uncontrolled hypertension \[blood pressure of \>/=140/90 mmHg on medication\], New York Heart Association (NYHA) Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), significant vascular disease (e.g., aortic aneurysm, aortic dissection) or Class II or greater peripheral vascular disease, history of stroke or TIA within 6 months prior to study enrollment, history of hypertensive crisis or hypertensive encephalopathy.
• History of active angina or myocardial infarction within 6 months. History of significant ventricular arrhythmia requiring medication with antiarrhythmics, or a history of a clinically significant conduction system abnormality.
• Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol.
• History or evidence upon physical examination of CNS disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)
• Prior history of pulmonary embolism or deep venous thrombosis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Bevacizumab; Erlotinib Hydrochloride; Capecitabine; 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; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Sunil Krishnan, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 13, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 1, 2016

Record last verified: 2016-07

Locations

US (1)