PRIME: Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00364013
First received: August 10, 2006
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to determine the treatment effect of panitumumab in combination with FOLFOX compared to FOLFOX alone as first line therapy for metastatic colorectal cancer


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Panitumumab
Drug: FOLFOX regimen
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: A Randomized, Multicenter, Phase 3 Study to Compare the Efficacy of Panitumumab in Combination With Oxaliplatin/ 5-fluorouracil/ Leucovorin to the Efficacy of Oxaliplatin/ 5-fluorouracil/ Leucovorin Alone in Patients With Previously Untreated Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: From randomization until the data cutoff date of 30 September 2008. Maximum follow-up time was 109 weeks. ] [ Designated as safety issue: No ]
    Progression-free survival (PFS), assessed by central radiological assessment, was defined as the time from randomization to disease progression per modified response evaluation criteria in solid tumors (RECIST) criteria or death. Participants who were alive but did not meet criteria for progression by the data cutoff date were censored at their last evaluable disease assessment date. Progressive disease is defined as a ≥ 20% increase in the size of target lesions or unequivocal progression of existing non-target lesions or any new lesions.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization until the data cutoff date of 28 August 2009. Maximum time on follow-up was 153 weeks. ] [ Designated as safety issue: No ]
    The definition of overall survival is the time from randomization to death; participants who were alive at the analysis data cutoff were censored at their last contact date.

  • Percentage of Participants With an Objective Response [ Time Frame: Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks. ] [ Designated as safety issue: No ]
    Participants were evaluated for tumor response per the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria every 8 weeks until disease progression. Objective response by central radiological assessment was defined as the incidence of either a confirmed complete or partial response (CR or PR) while on the first-line treatment, as determined by blinded independent central review and confirmed no less than 4-weeks after the criteria for response are first met. CR: Disappearance of all target and non-target lesions and no new lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions and no progression of non-target or no new lesions, or, disappearance of all target lesions and the persistence of ≥ 1 non-target lesion not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders.

  • Time to Progression [ Time Frame: From randomization until the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks. ] [ Designated as safety issue: No ]
    Time to progression was defined as time from randomization date to date of disease progression per the modified RECIST criteria.

  • Duration of Response [ Time Frame: Every 8 weeks until disease progression up to the data cut-off date of 30 September 2008; Maximum follow-up time was 109 weeks. ] [ Designated as safety issue: No ]
    Duration of response was calculated only for those participants with a confirmed CR or PR, as the time from the first CR or PR (subsequently confirmed within no less than 4 weeks) to first observed disease progression per modified RECIST criteria, based on a blinded central review.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: From randomization until the data cut-off date of 28 August 2009; Maximum time on follow-up was 153 weeks. ] [ Designated as safety issue: No ]
    A serious adverse event (SAE) is defined as an AE that • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard. The relationship of the adverse event to the study treatment was assessed by the Investigator by means of the question: "Is there a reasonable possibility that the event may have been caused by the study treatment?"


Enrollment: 1183
Study Start Date: August 2006
Study Completion Date: March 2013
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFOX + Panitumumab
Participants received panitumumab, 6 mg/kg on Day 1 and FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or unacceptable toxicity.
Drug: Panitumumab
Panitumumab 6 mg/kg over on Day 1 of each 14-day cycle, just prior to the administration of chemotherapy.
Other Name: Vectibix®
Drug: FOLFOX regimen
The FOLFOX regimen consisted of oxaliplatin 85 mg/m^2 intravenous (IV) infusion on Day 1, leucovorin, 200 mg/m^2 (racemate) on Days 1 and 2 and 5-fluorouracil 400 mg/m^2 IV bolus followed by 600 mg/m^2 IV infusion over 22 hours on Days 1 and 2. Each cycle was 14 days.
Active Comparator: FOLFOX
Participants received FOLFOX chemotherapy regimen on Days 1 and 2 of each 14-day cycle until disease progression or until unacceptable toxicity.
Drug: FOLFOX regimen
The FOLFOX regimen consisted of oxaliplatin 85 mg/m^2 intravenous (IV) infusion on Day 1, leucovorin, 200 mg/m^2 (racemate) on Days 1 and 2 and 5-fluorouracil 400 mg/m^2 IV bolus followed by 600 mg/m^2 IV infusion over 22 hours on Days 1 and 2. Each cycle was 14 days.

  Eligibility

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

Inclusion Criteria:

  • Man or woman at least 18 years old
  • Diagnosis of metastatic colorectal cancer
  • At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Paraffin-embedded tumor tissue from the primary tumor or metastasis available for central analyse Exclusion Criteria:
  • History or known presence of central nervous system (CNS) metastases
  • History of another primary cancer, except: Curatively treated in situ cervical cancer, or Curatively resected non-melanoma skin cancer, or Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization
  • Prior chemotherapy or systemic therapy for the treatment of metastatic colorectal carcinoma except: adjuvant fluoropyrimidine-based chemotherapy or prior fluoropyrimidine therapy administered solely for the purpose of radiosensitization
  • Prior oxaliplatin therapy
  • Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (eg, cetuximab) or treatment with small molecule EGFr inhibitors (eg, erlotinib)
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 1 year prior to randomization History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
  • Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > Common terminology criteria (CTC) grade 2 [CTCAE version 3.0])
  • Peripheral sensory neuropathy with functional impairment
  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: NCT00364013

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

Additional Information:
Publications:
Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Martin Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. Journal of Clinical Oncology;2010 Nov 1;28(31):4697-4705

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00364013     History of Changes
Other Study ID Numbers: 20050203
Study First Received: August 10, 2006
Results First Received: February 13, 2014
Last Updated: July 14, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Belgium: Directorate general for the protection of Public health
Brazil: Ministry of Health
Chile: Instituto de Salud Pública de Chile
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Hungary: National Institute of Pharmacy
Latvia: State Agency of Medicines
Mexico: Federal Commission for Protection Against Health Risks
Poland: Ministry of Health
South Africa: Department of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Canada: Health Canada

Keywords provided by Amgen:
Oncology
Cancer
metastatic colorectal cancer
EGFr
Panitumumab
Clinical Trail
Amgen

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
Fluorouracil
Oxaliplatin
Antibodies, Monoclonal
Leucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 29, 2014