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

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00613730
• Collaborator: (none)
• Enrollment: 3
• Arm: 1
• Duration (Months): 27

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer of Pancreas; Cancer of the Pancreas; Pancreas Cancer; Pancreatic Cancer	Drug: Gemcitabine; Drug: panitumumab	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jan 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall Survival at 1 Year [12 months]

   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

1. Progression-free Survival [Up to 25 months]

   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.

2. Percentage of Participants With Overall Response [Overall study]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00613730
• Other Study ID Numbers: 20060542
• First Posted: Feb 13, 2008
• Last Update Posted: Jan 6, 2014
• Last Verified: Nov 1, 2013

• Additional relevant MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Gemcitabine; Panitumumab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 26 March 2007 through 13 April 2007

Arm/Group Title	Gemcitabine + Panitumumab
Arm/Group 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.
Period Title: Overall Study
STARTED	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Gemcitabine + Panitumumab
Arm/Group 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.
Overall Participants	3
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	2 66.7%
Male	1 33.3%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	1 33.3%
White or Caucasian	2 66.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was terminated after enrolling 3 participants. This outcome was not evaluated.

Arm/Group Title	Gemcitabine + Panitumumab
Arm/Group 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.
Measure Participants	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was terminated after enrolling 3 participants. This outcome was not evaluated.

Arm/Group Title	Gemcitabine + Panitumumab
Arm/Group 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.
Measure Participants	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Study was terminated after enrolling 3 participants. This outcome was not evaluated.

Arm/Group Title	Gemcitabine + Panitumumab
Arm/Group 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.
Measure Participants	0

Adverse Events

Time Frame	First dose through maximum of safety follow-up or 30 days after last dose, up to 25 months.
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Gemcitabine + Panitumumab
Arm/Group 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.
All Cause Mortality
	Gemcitabine + Panitumumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine + Panitumumab
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
General disorders
Asthenia	1/3 (33.3%)
Hepatobiliary disorders
Bile duct obstruction	1/3 (33.3%)
Hyperbilirubinaemia	1/3 (33.3%)
Metabolism and nutrition disorders
Decreased appetite	1/3 (33.3%)
Dehydration	1/3 (33.3%)
Hyperglycaemia	1/3 (33.3%)
Hyponatraemia	1/3 (33.3%)
Renal and urinary disorders
Renal failure acute	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory distress	1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Gemcitabine + Panitumumab
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Blood and lymphatic system disorders
Anaemia	1/3 (33.3%)
Leukopenia	1/3 (33.3%)
Neutropenia	1/3 (33.3%)
Thrombocytopenia	1/3 (33.3%)
Cardiac disorders
Tachycardia	1/3 (33.3%)
Eye disorders
Erythema of eyelid	1/3 (33.3%)
Eye disorder	1/3 (33.3%)
Retinal oedema	1/3 (33.3%)
Gastrointestinal disorders
Abdominal pain	1/3 (33.3%)
Constipation	1/3 (33.3%)
Diarrhoea	1/3 (33.3%)
Dysphagia	1/3 (33.3%)
Mouth ulceration	1/3 (33.3%)
General disorders
Asthenia	1/3 (33.3%)
Chest pain	1/3 (33.3%)
Fatigue	1/3 (33.3%)
Mucosal inflammation	1/3 (33.3%)
Oedema	1/3 (33.3%)
Oedema peripheral	1/3 (33.3%)
Pyrexia	1/3 (33.3%)
Hepatobiliary disorders
Cholangitis	1/3 (33.3%)
Infections and infestations
Bacterial sepsis	1/3 (33.3%)
Paronychia	1/3 (33.3%)
Respiratory tract infection	1/3 (33.3%)
Upper respiratory tract infection	1/3 (33.3%)
Injury, poisoning and procedural complications
Fall	1/3 (33.3%)
Skin laceration	1/3 (33.3%)
Investigations
Weight decreased	1/3 (33.3%)
Metabolism and nutrition disorders
Dehydration	1/3 (33.3%)
Hyperglycaemia	1/3 (33.3%)
Hypokalaemia	2/3 (66.7%)
Hypomagnesaemia	1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)
Muscle spasms	1/3 (33.3%)
Nervous system disorders
Amnesia	1/3 (33.3%)
Encephalopathy	1/3 (33.3%)
Somnolence	1/3 (33.3%)
Psychiatric disorders
Anxiety	2/3 (66.7%)
Confusional state	1/3 (33.3%)
Disorientation	1/3 (33.3%)
Hallucination	1/3 (33.3%)
Renal and urinary disorders
Acute prerenal failure	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/3 (33.3%)
Oropharyngeal pain	1/3 (33.3%)
Respiratory tract congestion	1/3 (33.3%)
Rhinorrhoea	1/3 (33.3%)
Sputum increased	1/3 (33.3%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/3 (33.3%)
Dry skin	1/3 (33.3%)
Rash	1/3 (33.3%)
Skin fissures	1/3 (33.3%)
Vascular disorders
Hypotension	1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial resul