Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy of Neoadjuvant Chemoradiation for Potentially Resectable Pancreas Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00557492
First received: November 13, 2007
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

This study is to determine the efficacy of bevacizumab and gemcitabine in combination with radiation therapy in the preoperative treatment of potentially-resectable subjects with pancreatic cancer.


Condition Intervention Phase
Pancreatic Cancer
Drug: Avastin (bevacizumab)
Drug: Gemzar (Gemcitabine)
Radiation: external beam radiotherapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the Anti-Vascular Endothelial Growth Factor (α-VEGF) Monoclonal Antibody Bevacizumab in Combination With Fixed Dose Rate (FDR) Gemcitabine and Rapid-Fractionation Radiotherapy in the Pre-operative Treatment of Potentially- Resectable Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • To determine the rate of margin negative surgical resection (R0 resection rate), and to establish the rate of complete pathologic response in resected pancreas cancer after neoadjuvant treatment. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of surgical resection, treatment drop-out due to toxicity, and disease progression during treatment. Radiographic tumor response, biomarker response, first site of tumor recurrence, overall and disease-free survival, pre- to post-treatment change in [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: December 2006
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Avastin (bevacizumab)
    10 mg/kg, days 1, 15, 29 and 43
    Drug: Gemzar (Gemcitabine)
    On days 1, 15, and 29, subjects will receive gemcitabine 1500 mg/m2 IV over 150 minutes at the fixed-dose rate (10 mg/m2/min).
    Radiation: external beam radiotherapy
    3 Gy/fraction utilizing a 95% isodose field over 10 consecutive weekdays, Monday to Friday, for a total of 30 Gy
Detailed Description:

This is a 2 stage phase II study of bevacizumab (10 mg/kg) and fixed dose rate (FDR) gemcitabine (1500 mg/m2 at 10 mg/kg/min) in combination with sequential rapid fractionation radiotherapy (30 Gy total) in the preoperative treatment of potentially-resectable subjects with adenocarcinoma of the pancreas. The purpose of this study is to determine the rate of margin negative surgical resection (R0 resection rate) and the rate of complete pathological response in patients with resected pancreas cancer. The overall goal of this study is to determine the merit of this novel regimen for further study in a Phase III trial examining time to progression and overall survival. Based on the need for 48 evaluable subjects to evaluate the primary endpoints, the study will be opened with a target accrual of 60 subjects given an expected 20% rate of attrition observed in prior studies of subjects with pancreas cancer at UPCI.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic or cytologic proof of pancreatic adenocarcinoma.
  • Subjects with biopsy-proven adenocarcinoma of the pancreas which is potentially resectable by preoperative imaging. Subjects will be considered potentially resectable using criteria defined by Pisters (Pisters et al., 2001):
  • if imaging detects no evidence of extrapancreatic disease;
  • no evidence of tumor extension to the superior mesenteric artery (SMA) or celiac axis (intact fat plane between the tumor and the adjacent visceral artery),
  • patent superior mesenteric-portal vein confluence
  • no encasement of portal or superior mesenteric vein.
  • Karnofsky performance status ≥ 80.
  • No active second malignancy except for basal cell carcinoma of the skin
  • Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced by:
  • Serum creatinine level ≤1.6 mg/dl ( Calculated Creat clearance >50)
  • Serum total bilirubin level ≤1.5 X ULN
  • Urine protein excretion ≤ 1+ by urine dipstick
  • White blood cell count ≥ 3.5x109/ml per ml and platelet count ≥ 100x109 per ml
  • Age >18 years.
  • Children are excluded because of toxic effects of bevacizumab and gemcitabine on growth and development during preclinical studies.
  • For subjects with obstructive jaundice, the biliary tract must be drained with a temporary plastic or a short permanent metallic biliary stent.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Disease-Specific Exclusions
  • Subjects who have received chemotherapy within 12 months prior to study entry.
  • Prior use of radiotherapy or investigational agents for pancreatic cancer.
  • Subjects who have undergone laparotomy for pancreas cancer within 6 weeks
  • Any evidence of metastasis to distant organs (liver, lung, peritoneum).
  • Symptomatic or endoscopic evidence of gastric outlet obstruction

    • Endoscopic findings suggesting tumor erosion into the gastrointestinal mucosa.

  • Concurrent malignancies with evidence of active or measurable disease except basal cell carcinoma of the skin.
  • General Medical Exclusions
  • Inability to adhere to study and/or follow-up procedures
  • History of allergic reactions or hypersensitivity to the study drugs (bevacizumab, gemcitabine, and proton pump inhibitors).
  • Other concurrent experimental therapy.
  • Because subjects with immune deficiency are at increased risk for lethal infections when treated with marrow-suppressive therapy, HIV-positive subjects receiving combination anti-retroviral therapy are excluded from the study.
  • Bevacizumab-Specific Exclusions
  • Subjects who have had recent surgery (prior 6 weeks)
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • Subjects with the following co-morbid medical conditions:
  • History of myocardial infarction or unstable angina within 12 months prior to study enrollment.
  • Ascites
  • Pregnancy/lactation - The effects of the study drugs on the developing human fetus are unknown. For this reason and because bevacizumab, gemcitabine, and radiation therapy used in this trial are known to be teratogenic in animal studies, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of study entry until 6 months after the completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A serum pregnancy test for those females of childbearing potential must be done prior to their receiving study drugs. Due to the combined effects of chemotherapy and radiation, breastfeeding is not allowed for 6 months after the completion of study participation.
  • Regular aspirin use > 325 mg per day
  • Regular NSAID use
  • Bleeding diathesis, coagulopathy, need for full-dose anticoagulation or INR > 1.5
  • Known central nervous system metastasis
  • Previous cerebrovascular accident, transient ischemic attack, or seizure (within 6 months)
  • Serious non-healing wound, ulcer, or bone fracture
  • History of abdominal fistula, gastrointestinal perforation, diverticulitis, or intra-abdominal abscess within 6 months prior to study enrollment.
  • Recent hemoptysis,
  • Uncontrolled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) grade 2 or greater congestive heart failure (see Appendix I)
  • Prior deep venous thrombosis or pulmonary embolism
  • Urine protein excretion 2+ or ≥ 1 g per 24 hours
  • Peripheral vascular disease such as lower extremity claudication and rest pain or prior lower extremity vascular surgery for arterial insufficiency
  • Dyspnea requiring supplemental oxygen
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557492

Locations
United States, Pennsylvania
University of Pittsburgh Medical Centers
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Herbert J. Zeh, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00557492     History of Changes
Obsolete Identifiers: NCT00428324
Other Study ID Numbers: 06-035
Study First Received: November 13, 2007
Last Updated: October 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
pancreas
pancreatic
cancer
resectable

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Bevacizumab
Gemcitabine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014