Gemcitabine and Pazopanib in Metastatic Pancreatic Cancer

This study has been terminated.
(Closed due to delay by GSK)
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01080248
First received: March 2, 2010
Last updated: July 22, 2013
Last verified: July 2013
  Purpose

To determine the response rate and survival of gemcitabine and pazopanib in patients with metastatic pancreatic cancer.


Condition Intervention Phase
Pancreatic Cancer
Drug: Gemcitabine
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Gemcitabine and Pazopanib in Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • To determine the response rate by RECIST criteria. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the progression free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine the median survival and overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: August 2010
Study Completion Date: October 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1

Gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 of each 28 day cycle.

Pazopanib 800 mg PO daily of each 28 day cycle.

Drug: Gemcitabine
Other Name: Gemzar
Drug: Pazopanib
Other Name: Votrient

Detailed Description:

To determine the response rate by RECIST criteria.

To determine the progression free survival.

To determine the median survival and overall survival at one year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have a histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma.
  • Patient must have metastatic disease that is not amenable to surgical resection.
  • Patient must have measurable disease (by RECIST criteria), defined as at least one lesion that can be accurately measured in at least one dimension.
  • Patient may have previously untreated disease or may have been previously treated if they meet the following criteria:

    • received adjuvant gemcitabine therapy >6 months prior to enrollment with progression off therapy
    • received prior radiation therapy > 4 weeks prior to study enrollment and have measurable tumor mass outside the radiation field
    • received prior radiation therapy > 4 weeks prior to study enrollment, have a measurable tumor mass outside the radiation field, and received 5-FU as a radiation sensitizer >4 weeks prior to study enrollment
  • Patient must be >=18 years old. Note: pazopanib is contraindicated in the pediatric population due to the potential effect on the epiphyseal growth plates.
  • Patient must have an ECOG performance status of 0-1
  • Patient must have normal organ and marrow function within 14 days of study initiation as defined below:

    • ANC ≥ 1.5 x 109/L
    • Hemoglobin ≥ 9 g/dL; patients may not have had a transfusion within 7 days of screening assessment
    • Platelets ≥ 100 x 109/L
    • PT or INR ≤ 1.2 x upper limit of normal (ULN)
    • PTT ≤ 1.2 x ULN
    • Total bilirubin ≤ 1.5 x ULN
    • AST and ALT ≤ 2.5 x ULN
    • Serum creatinine ≤ 1.5 mg/dL; if > 1.5 mg/dL, calculated creatinine clearance must be ≥ 50 mL/min
    • Urine protein to creatinine ratio < 1; if ≥ 1, then a 24-hour urine protein must be assessed and must be < 1 g in order for patients to be eligible
  • Patient must have the ability to understand and the willingness to sign a written informed consent document.
  • Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods.

Exclusion Criteria

  • Patient has been treated with an agent that antagonizes the VEGF receptor.
  • Patient has received any other investigational agents < 28 days prior to enrollment.
  • Patient has known brain metastases; these patients are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. In addition, patients with brain metastases may be at a higher theoretical risk for cerebral hemorrhage while taking pazopanib.
  • Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib, gemcitabine, or other agents used in the study.
  • Patient has an increased risk of hemorrhage such as having received thrombolytic agents within the past month, being on an unstable dose of anticoagulation, or having a known bleeding diathesis.
  • Patient has a clinically significant gastrointestinal abnormality that may increase the risk for GI bleeding such as:

    • Active inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease) or other gastrointestinal conditions with increased risk of perforation
    • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess ≤ 28 days prior to beginning study treatment
  • Patient has a history of any one or more of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Coronary artery by-pass graft surgery
    • Symptomatic peripheral vascular disease
    • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  • Patient has prolonged QT intervals, taking antiarrhythmics or taking other medications that prolong QT
  • Patient has poorly controlled hypertension (defined as systolic blood pressure (SBP) of ≥160 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg). Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
  • Patient has a history of cerebrovascular accident, pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6 months.
  • Patient has had major surgery, trauma, non-healing wound, fracture, or ulcer within 28 days prior to first dose of gemcitabine and/or study drug (procedures such as catheter placement not considered to be major) OR minor surgery within 14 days prior to first dose of gemcitabine and/or study drug.
  • Patient has significant proteinuria as evidenced by urine protein/creatinine ratio >1
  • Patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, active second malignancy, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patient is pregnant or breastfeeding. Pregnant women are excluded from this study because pre-clinical reproductive toxicity studies with pazopanib demonstrated reduced female fertility and teratogenic effects.
  • Patient is known HIV-positive. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • Patient is a known alcohol, cocaine, or IV drug abuser within 6 months prior to enrollment.
  • Patient is receiving treatment with any of the following anti-cancer therapies:

    • Radiation therapy, surgery, or tumor embolization within 4 weeks prior to the first dose of pazopanib OR
    • Chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy within 28 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib.
  • Patient is experiencing any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity.
  • Inclusion of Women and Minorities
  • Both men and women and members of all races and ethnic groups are eligible for this trial.
  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: NCT01080248

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Joel Picus, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01080248     History of Changes
Other Study ID Numbers: 10-0434 / 201103201
Study First Received: March 2, 2010
Last Updated: July 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Pancreas

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
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 October 22, 2014