Adenocarcinoma of the Pancreas Treated With Panitumumab and Gemcitabine Regimen to Investigate Overall Survival as Primary Endpoint (APPRISE 1)

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

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer; Pancreas Cancer; Cancer of Pancreas; Cancer of the Pancreas
• Intervention / Treatment: Drug: Gemcitabine; Drug: 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).

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Gemcitabine + panitumumab; 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.

Drug: Gemcitabine; Intravenous administration; Other Names: Gemzar; Drug: panitumumab; Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 25 months
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.	Overall study

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: January 31, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Estimate): January 6, 2014
• Last Update Submitted That Met QC Criteria: November 15, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Gemcitabine; Panitumumab
• Other Study ID Numbers: 20060542