Adenocarcinoma of the Pancreas Treated With Panitumumab and Gemcitabine Regimen to Investigate Overall Survival as Primary Endpoint (APPRISE 1)
Primary Purpose
Cancer of Pancreas, Cancer of the Pancreas, Pancreas Cancer
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Gemcitabine
panitumumab
Sponsored by
About this trial
This is an interventional treatment trial for Cancer of Pancreas
Eligibility Criteria
Inclusion Criteria:
- Men or women ≥ 18 and ≤ 75 years of age
- Histologically or cytologically confirmed pancreatic adenocarcinoma meeting one of the following criteria: Locally advanced unresectable disease, or metastatic disease
- Measurable or unmeasurable disease
- Patients with unresectable pancreatic cancer who have had surgery (exploratory laparotomy, bilary, gastrointestinal bypass) are eligible, if the patient has fully recovered from surgery and ≥ 28 days has passed since the operation. Patients with history of pancreatoduodenectomy are eligible provided that there is radiographically documented disease recurrence
- Karnofsky performance score ≥ 60 %
- Life expectancy of ≥ 12 weeks as documented by the investigator
- Hematologic function, as follows: Absolute neutrophils count (ANC) ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, and hemoglobin ≥ 9.0 g/dL
- Renal function, as follows: Serum creatinine ≤ 1.5 mg/dL
- Hepatic function, as follows: Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (if liver metastases ≤ 5 x ULN), alanine aminotransferase (ALT) ≤ 3 x ULN (if liver metastases ≤ 5 x ULN), and total bilirubin ≤ 2.0 mg/dL. Patients with history of biliary obstruction are eligible after intervention, once this criteria is met.
- Metabolic function, as follows: Magnesium ≥ lower limit of normal, and calcium ≥ lower limit of normal
- Competent to comprehend, sign, and date an International Ethics Committee/Institutional Review board (IEC/IRB)-approved informed consent form
Exclusion Criteria:
- Islet cell or acinar cell carcinoma or cystadenocarcinoma
- History or known presence of central nervous system (CNS) mestatases
- History of another primary cancer, except: Curatively treated cervical carcinoma in situ, or curatively resected non-melanomatous skin cancer, or other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 3 years prior to enrollment
- Other concurrent anticancer chemotherapy
- Concomitant malignant disease
- Prior radiotherapy ≤ 14 days, or if subjects has not recovered from radiotherapy
- Uncontrolled seizure disorder or other serious neurological diseases
- Any co-morbid disease that would increase risk of toxicity
- Prior anti-Epidermal growth factor receptor (EGFr) antibody or Vascular endothelial growth factor (VEGF) therapy (eg, cetuximab, bevacizumab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib)
- Adjuvant chemotherapy or chemoradiotherapy ≥ 24 weeks prior to enrollment
- Prior treatment with gemcitabine
- Patients requiring chronic use of immunosuppressive agents (eg, methotrexate, cyclosporine, corticosteroids)
- Regular use (as determined by the investigator) of nonsteroidal anti-inflammatory agents
- Known allergy to panitumumab or any components of panitumumab formulation or gemcitabine
- Recent infection requiring a course of systemic anti-infectives that was completed ≤ 14 days before enrollment (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection [UTI])
- Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year prior to enrollment
- History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease) on screening chest x-ray or computed tomography (CT) scan
- Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤ 8 weeks prior to enrollment
- Pre-existing bleeding diathesis or coagulopathy with the exception of well-controlled chronic anticoagulation (eg, coumadin or heparin therapy). Patients receiving coumadin should have their International Normalized Ratio (INR) monitored closely
- History of any medical or psychiatric condition or addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
- Patient unwilling or unable to comply with study requirements
- Patient who is pregnant or breast feeding
- Man or woman of child bearing potential (women who are post menopausal < 52 weeks, not surgically sterilized, or not abstinent) who do not consent to use adequate contraceptive precautions (per institutional standard of care) during the course of the study and for 24 weeks for women and 4 weeks for men, after the last dose of gemcitabine or panitumumab, whichever dose is last
- Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
- Major surgery ≤ 28 days or minor surgery ≤ 14 days prior to enrollment
- Documented history of alcohol, cocaine or intravenous drug abuse ≤ 6 months of enrollment
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Gemcitabine + panitumumab
Arm Description
Panitumumab 6 mg/kg was administered intravenously (IV) before gemcitabine on Day 1 of Weeks 1, 3, 5, and 7, and then every 2 weeks (day 1 and 15) of each subsequent 4-week chemotherapy cycle. Gemcitabine 1000 mg/m^2 was administered IV once weekly (on Day 1) for 7 weeks, followed by a 1-week rest period. In subsequent cycles, gemcitabine was given once weekly (on Day 1) for 3 consecutive weeks followed by 1 week of rest. Panitumumab and gemcitabine treatment continued until disease progression, unacceptable adverse events, death, or study withdrawal occurred.
Outcomes
Primary Outcome Measures
Overall Survival at 1 Year
The survival time is calculated from Study Day
1 (ie, the first day that a participant receives study treatment with the gemcitabine regimen in combination with panitumumab) to the date of death due to any cause.
Secondary Outcome Measures
Progression-free Survival
Progression-Free Survival was defined as the time from Study Day 1 to the date of disease progression or the date of death due to any cause (whichever comes earlier). Disease progression is determined per Response Evaluation Criteria in Solid Tumors (RECIST) criteria or per physician's assessment based on symptom progression.
Percentage of Participants With Overall Response
Overall Response defined as the percentage of participants with complete or partial response (CR or PR), as defined by modified RECIST. CR: Disappearance of all target and non-target lesions. PR: Either at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameters (SLD) and no progression of existing non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00613730
Brief Title
Adenocarcinoma of the Pancreas Treated With Panitumumab and Gemcitabine Regimen to Investigate Overall Survival as Primary Endpoint
Acronym
APPRISE 1
Official Title
Phase II, Multi-center, Open-label, Single-Arm Study Using Gemcitabine and Panitumumab in the First-line Treatment of Subjects With Locally Advanced Unresectable or Metastatic Adenocarcinoma of the Pancreas
Study Type
Interventional
2. Study Status
Record Verification Date
November 2013
Overall Recruitment Status
Terminated
Why Stopped
APPRISE closure prompted by SWOG S0205 not meeting primary endpoint-improving OS. APPRISE enrollment closure due to similar design;no unexpected safety data
Study Start Date
January 2007 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
This is a phase II, multi-center, open-label, single-arm clinical trial to be conducted in the United States. In approximately 55 centers, approximately 75 eligible locally advanced unresectable or metastatic pancreatic cancer subjects will be enrolled to receive first-line therapy of gemcitabine and panitumumab.
Detailed Description
Enrollment closed after 3 patients were enrolled. This voluntary action was prompted by the announcement that the Southwest Oncology Group (SWOG) S0205 trial (NCT00075686), A Phase III Randomized Open Label Study Comparing Gemcitabine Plus Cetuximab (IMC-C225) Versus Gemcitabine as First-Line Therapy of Patients with Advanced Pancreas Cancer, did not meet its primary endpoint of improving overall survival).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer of Pancreas, Cancer of the Pancreas, Pancreas Cancer, Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gemcitabine + panitumumab
Arm Type
Experimental
Arm Description
Panitumumab 6 mg/kg was administered intravenously (IV) before gemcitabine on Day 1 of Weeks 1, 3, 5, and 7, and then every 2 weeks (day 1 and 15) of each subsequent 4-week chemotherapy cycle. Gemcitabine 1000 mg/m^2 was administered IV once weekly (on Day 1) for 7 weeks, followed by a 1-week rest period. In subsequent cycles, gemcitabine was given once weekly (on Day 1) for 3 consecutive weeks followed by 1 week of rest. Panitumumab and gemcitabine treatment continued until disease progression, unacceptable adverse events, death, or study withdrawal occurred.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Intravenous administration
Intervention Type
Drug
Intervention Name(s)
panitumumab
Intervention Description
Intravenous administration
Primary Outcome Measure Information:
Title
Overall Survival at 1 Year
Description
The survival time is calculated from Study Day
1 (ie, the first day that a participant receives study treatment with the gemcitabine regimen in combination with panitumumab) to the date of death due to any cause.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Progression-Free Survival was defined as the time from Study Day 1 to the date of disease progression or the date of death due to any cause (whichever comes earlier). Disease progression is determined per Response Evaluation Criteria in Solid Tumors (RECIST) criteria or per physician's assessment based on symptom progression.
Time Frame
Up to 25 months
Title
Percentage of Participants With Overall Response
Description
Overall Response defined as the percentage of participants with complete or partial response (CR or PR), as defined by modified RECIST. CR: Disappearance of all target and non-target lesions. PR: Either at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameters (SLD) and no progression of existing non-target lesions and no new lesions, or, the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.
Time Frame
Overall study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men or women ≥ 18 and ≤ 75 years of age
Histologically or cytologically confirmed pancreatic adenocarcinoma meeting one of the following criteria: Locally advanced unresectable disease, or metastatic disease
Measurable or unmeasurable disease
Patients with unresectable pancreatic cancer who have had surgery (exploratory laparotomy, bilary, gastrointestinal bypass) are eligible, if the patient has fully recovered from surgery and ≥ 28 days has passed since the operation. Patients with history of pancreatoduodenectomy are eligible provided that there is radiographically documented disease recurrence
Karnofsky performance score ≥ 60 %
Life expectancy of ≥ 12 weeks as documented by the investigator
Hematologic function, as follows: Absolute neutrophils count (ANC) ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, and hemoglobin ≥ 9.0 g/dL
Renal function, as follows: Serum creatinine ≤ 1.5 mg/dL
Hepatic function, as follows: Aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) (if liver metastases ≤ 5 x ULN), alanine aminotransferase (ALT) ≤ 3 x ULN (if liver metastases ≤ 5 x ULN), and total bilirubin ≤ 2.0 mg/dL. Patients with history of biliary obstruction are eligible after intervention, once this criteria is met.
Metabolic function, as follows: Magnesium ≥ lower limit of normal, and calcium ≥ lower limit of normal
Competent to comprehend, sign, and date an International Ethics Committee/Institutional Review board (IEC/IRB)-approved informed consent form
Exclusion Criteria:
Islet cell or acinar cell carcinoma or cystadenocarcinoma
History or known presence of central nervous system (CNS) mestatases
History of another primary cancer, except: Curatively treated cervical carcinoma in situ, or curatively resected non-melanomatous skin cancer, or other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 3 years prior to enrollment
Other concurrent anticancer chemotherapy
Concomitant malignant disease
Prior radiotherapy ≤ 14 days, or if subjects has not recovered from radiotherapy
Uncontrolled seizure disorder or other serious neurological diseases
Any co-morbid disease that would increase risk of toxicity
Prior anti-Epidermal growth factor receptor (EGFr) antibody or Vascular endothelial growth factor (VEGF) therapy (eg, cetuximab, bevacizumab) or treatment with small molecule EGFr inhibitors (eg, gefitinib, erlotinib, lapatinib)
Adjuvant chemotherapy or chemoradiotherapy ≥ 24 weeks prior to enrollment
Prior treatment with gemcitabine
Patients requiring chronic use of immunosuppressive agents (eg, methotrexate, cyclosporine, corticosteroids)
Regular use (as determined by the investigator) of nonsteroidal anti-inflammatory agents
Known allergy to panitumumab or any components of panitumumab formulation or gemcitabine
Recent infection requiring a course of systemic anti-infectives that was completed ≤ 14 days before enrollment (exception can be made at the judgment of the investigator for oral treatment of an uncomplicated urinary tract infection [UTI])
Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year prior to enrollment
History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease) on screening chest x-ray or computed tomography (CT) scan
Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤ 8 weeks prior to enrollment
Pre-existing bleeding diathesis or coagulopathy with the exception of well-controlled chronic anticoagulation (eg, coumadin or heparin therapy). Patients receiving coumadin should have their International Normalized Ratio (INR) monitored closely
History of any medical or psychiatric condition or addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
Patient unwilling or unable to comply with study requirements
Patient who is pregnant or breast feeding
Man or woman of child bearing potential (women who are post menopausal < 52 weeks, not surgically sterilized, or not abstinent) who do not consent to use adequate contraceptive precautions (per institutional standard of care) during the course of the study and for 24 weeks for women and 4 weeks for men, after the last dose of gemcitabine or panitumumab, whichever dose is last
Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
Major surgery ≤ 28 days or minor surgery ≤ 14 days prior to enrollment
Documented history of alcohol, cocaine or intravenous drug abuse ≤ 6 months of enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Adenocarcinoma of the Pancreas Treated With Panitumumab and Gemcitabine Regimen to Investigate Overall Survival as Primary Endpoint
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