PACCE: Panitumumab Advanced Colorectal Cancer Evaluation Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00115765
First received: June 26, 2005
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to assess whether treatment with the study drug, panitumumab given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive concomitant panitumumab therapy.


Condition Intervention Phase
Colorectal Cancer
Drug: Oxaliplatin Based Chemotherapy
Drug: Panitumumab
Drug: Irinotecan Based Chemotherapy
Drug: Bevacizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PACCE: A Randomized, Open-Label, Controlled, Clinical Trial of Chemotherapy and Bevacizumab With and Without Panitumumab in the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression-Free Survival (Oxaliplatin) [ Time Frame: Overall study ] [ Designated as safety issue: No ]
    Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression

  • Objective Tumor Response Through Week 12 (Irinotecan) [ Time Frame: Overall Study ] [ Designated as safety issue: No ]
    Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum


Secondary Outcome Measures:
  • Overall Survival (Oxaliplatin) [ Time Frame: Overall study ] [ Designated as safety issue: No ]
    Kaplan-Meier estimate of the median time from randomization to death from any cause in groups treated with Oxaliplatin

  • Objective Tumor Response Rate (Oxaliplatin) [ Time Frame: Overall study ] [ Designated as safety issue: No ]
    Best overall response of complete or partial response within oxaliplatin stratum

  • Time to Progression (Oxaliplatin) [ Time Frame: Overall Study ] [ Designated as safety issue: No ]
    Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the oxaliplatin stratum

  • Time to Treatment Failure (Oxaliplatin) [ Time Frame: Overall study ] [ Designated as safety issue: No ]
    Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the oxaliplatin stratum.

  • Overall Survival (Irinotecan) [ Time Frame: Overall study ] [ Designated as safety issue: No ]
    Incidence of mortality from any cause in groups treated with Irinotecan. Incidence is provided in lieu of the median time to death since the median or its measure of dispersion was not estimable for at least one treatment arm.

  • Progression-free Survival (Irinotecan) [ Time Frame: Overall Study ] [ Designated as safety issue: No ]
    Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression

  • Objective Tumor Response Rate (Irinotecan) [ Time Frame: Overall Study ] [ Designated as safety issue: No ]
    Best overall response of complete or partial response within irinotecan stratum

  • Time to Progression (Irinotecan) [ Time Frame: Overall Study ] [ Designated as safety issue: No ]
    Kaplan-Meier estimate of the median time from randomization to disease progression or death due to disease progression within the irinotecan stratum

  • Time to Treatment Failure (Irinotecan) [ Time Frame: Overall Study ] [ Designated as safety issue: No ]
    Kaplan-Meier estimate of the median time from randomization to the date the decision was made to discontinue treatment for a reason other than a complete response to treatment within the irinotecan stratum


Enrollment: 1053
Study Start Date: June 2005
Study Completion Date: December 2009
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Oxaliplatin and bevacizumab without panitumumab
Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone.
Drug: Oxaliplatin Based Chemotherapy
Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
  • FOLFOX 4
  • FOLFOX 5
  • Modified FOLFOX 6
  • FOLFOX 7
  • Oxaliplatin
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Name: Avastin
Experimental: Irinotecan and bevacizumab plus panitumumab
Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
Drug: Panitumumab
PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.
Other Names:
  • pmab
  • Vectibix
Drug: Irinotecan Based Chemotherapy
Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
  • FOLFIRI
  • Douillard
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Name: Avastin
Active Comparator: Irinotecan and bevacizumab without panitumumab
Irinotecan-based chemotherapy and Bevacizumab Q2W alone
Drug: Irinotecan Based Chemotherapy
Irinotecan-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) - Irinotecan, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
  • FOLFIRI
  • Douillard
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Name: Avastin
Experimental: Oxaliplatin and bevacizumab plus panitumumab
Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
Drug: Oxaliplatin Based Chemotherapy
Oxaliplatin-based Chemotherapy Every 2 Week Regimens (Q2W Cycles) consisting of Oxaliplatin, Leucovorin (LV), 5-Fluorouracil (5-FU) - To be determined by physician. On Day 1 irinotecan and LV are given at the same time using different bags and a Y-line followed by 5-FU administration.
Other Names:
  • FOLFOX 4
  • FOLFOX 5
  • Modified FOLFOX 6
  • FOLFOX 7
  • Oxaliplatin
Drug: Panitumumab
PanitumumabPanitumumab is a high affinity (Kd = 5 x 10-11 M) fully human IgG2 monoclonal antibody that is directed against the human EGFr. Panitumumab will be administered by a 30-60 minute IV infusion at a dose of 6 mg/kg once every 2 weeks on the same day of the oxaliplatin- or irinotecan-based chemotherapy and bevacizumab.
Other Names:
  • pmab
  • Vectibix
Drug: Bevacizumab
Bevacizumab is a vascular endothelial growth factor (VEGF)-targeted antibody therapy that was administered to subjects intravenously Q2 weeks as per usual standard of care on the same day of chemotherapy and panitumumab administration .
Other Name: Avastin

  Eligibility

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

Inclusion Criteria:

  • Adenocarcinoma of the colon or rectum
  • Metastatic colorectal cancer (mCRC)
  • Measurable disease per modified response evaluation criteria in solid tumors (RECIST) criteria
  • ECOG performance status of 0 or 1
  • Available paraffin-embedded tumor tissue (from primary tumor or metastasis) or unstained slides of paraffin-embedded tissue
  • If history of other primary cancer, subject will be eligible only if she or he has:

    • Curatively resected non-melanomatous skin cancer;
    • Curatively treated cervical carcinoma in situ;
    • Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 5 years.
  • Adequate hematologic data as follows:

    • Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9 cells/L;
    • Platelet count greater than or equal to 100 x 10^9/L;
    • Hemoglobin greater than or equal to 9.0 g/dL. - Adequate renal function:
    • Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN);
    • Urinary protein dipstick of less than 2+ (if urinary dipstick 2+ or greater, then excretion of less than or equal to 1000 mg of protein per day as determined by 24-hour urine collection).
  • Adequate hepatic function:

    • Alkaline phosphatase less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
    • Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)(AST) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
    • Alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
    • Bilirubin less than or equal to 2 x ULN. - Competent to comprehend, sign, and date an IRB-approved informed consent form
  • Before any study-specific procedure, the appropriate written informed consent must be obtained.

Exclusion Criteria:

  • Prior chemotherapy or biologic (i.e., antibody or vaccine) treatment for mCRC disease - Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before randomization - Radiotherapy within 14 days before randomization
  • Elective and/or planned major surgical procedure to be performed during the course of this trial (surgery that arises as needed or necessary during the course of the study, not agreed a priori, will not make the subject ineligible)
  • Major surgery within 28 days before randomization
  • Central nervous system metastases
  • History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan
  • Clinically significant ascites
  • Preexisting bleeding diathesis or coagulopathy or the need for full-dose anticoagulation
  • Any of the following within 1 year before randomization:

    • Myocardial infarction;
    • Unstable angina;
    • Symptomatic congestive heart failure;
    • Serious uncontrolled cardiac arrhythmia;
    • Cerebrovascular accident or transient ischemic attack;
    • Gastrointestinal ulcer or hemorrhage;
    • Hemoptysis;
    • Pulmonary embolism;
    • Deep vein thrombosis, or other significant thromboembolic event.
  • Regular use of non-steroidal anti-inflammatory agents
  • Female subject of childbearing potential, not abstinent, and not willing to use contraceptives during the course of the study and for 6 months following the last dose of first-line treatment
  • Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization
  • Male subject, not abstinent, and not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of first-line treatment
  • Subject known to be human immunodeficiency virus (HIV) positive
  • Subject allergic to panitumumab or any components of panitumumab formulation
  • History of any medical or psychiatric condition 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
  • Subject unwilling or unable to comply with study requirements
  • Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00115765

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00115765     History of Changes
Other Study ID Numbers: 20040249
Study First Received: June 26, 2005
Results First Received: August 19, 2010
Last Updated: June 13, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Amgen:
Panitumumab Advanced Colorectal Cancer Evaluation Study (PACCE Study)
Colorectal, Colon, Rectal Cancer, Metastatic Colorectal
Cancer
EGFr, Clinical Trial
Panitumumab, ABX-EGF
Immunex, Abgenix, Amgen
Metastatic Colorectal Cancer
Oncology

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Irinotecan
Bevacizumab
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunologic Factors

ClinicalTrials.gov processed this record on April 17, 2014