Panitumumab Plus FOLFIRI in First-line Treatment of Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00508404
First received: July 26, 2007
Last updated: December 18, 2015
Last verified: December 2015
  Purpose
To estimate the effect of KRAS mutation status (Wild-type versus Mutant) on objective response rate and other measures of efficacy for patients treated with panitumumab in combination with a chemotherapy regimen of irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line therapy for metastatic colorectal cancer (mCRC).

Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Panitumumab
Drug: FOLFIRI
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm Multicentre Phase II Study of Panitumumab in Combination With Irinotecan/5-fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks ] [ Designated as safety issue: No ]

    Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments are based on investigator review of scans using modified Response Evaluation Criteria in Solid Tumors (RECIST) V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders.

    Complete Response (CR): disappearance of all target and non-target lesions and no new lesions.

    Partial Response (PR): At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or progressive disease (PD) and no new lesions.



Secondary Outcome Measures:
  • Objective Response by 17 Weeks [ Time Frame: Up to Week 17 ] [ Designated as safety issue: No ]
    The percentage of participants with a best response of complete response or partial response by Week 17. Disease assessments are based on investigator review of scans using modified RECIST V1.0 criteria. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Participants with no post-baseline assessment were considered non-responders.

  • Disease Control Rate [ Time Frame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks ] [ Designated as safety issue: No ]

    The percentage of participants whose best response was either a complete or partial response or stable disease, based on modified RECIST v1.0 criteria as assessed by the Investigator.

    Stable diease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD of target lesions and no progression of existing non-target lesions and no new lesions, or, the persistence of 1 or more non-target lesions not qualifying for either CR or PD if no target lesions were identified at Baseline.


  • Duration of Response [ Time Frame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    Duration of response was calculated only for those participants who had a confirmed complete or partial response, and is defined as the time from first confirmed response to first observed progression. For participants who responded and did not progress by the analysis data cut-off date, duration of response was censored at their last evaluable disease assessment date. Duration of response was analyzed using the Kaplan-Meier method.

  • Time to Initial Objective Response [ Time Frame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    Time to response is the time from the date of enrollment to the date of first confirmed complete or partial response. Participants with a best response of stable disease at the analysis data cut-off date were censored at their last assessment of SD and participants with all other categories of best response were censored at the maximum observed time to a first confirmed response among all responders. Time to initial objective response was analyzed using Kaplan-Meier methods.

  • Progression-free Survival [ Time Frame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    Progression-free survival is the time from the date of enrollment to the date of first observed progression or death, whichever comes first. Participants who were alive and did not progress by the analysis data cut-off date were censored at the last evaluable disease assessment date. Progression-free survival was analyzed using Kaplan-Meier methods.

  • Time to Disease Progression [ Time Frame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    Time to progression is the time from the enrollment date to the date of first observed progression. For participants who had not progressed by the analysis data cutoff date, time to progressive disease was censored at their last evaluable disease assessment date. Time to disease progression was analyzed using Kaplan-Meier methods.

  • Duration of Stable Disease [ Time Frame: Tumor response was assessed at Week 8 and every 8 weeks to Week 48 and 3 monthly thereafter until disease progression; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    Duration of stable disease was calculated only for participants with a best response of stable disease and is defined as the time from enrollment to first observed PD. For participants who did not progress by the analysis data cut-off date, duration of SD was censored at their last evaluable disease assessment date. Duration of stable disease was estimated using Kaplan-Meier methods.

  • Time to Treatment Failure [ Time Frame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    Time to treatment failure is defined as the time from enrollment to the date the decision was made to end the treatment phase for any reason. For participants who remained in the treatment phase at the analysis data cut-off date, time to treatment failure was censored at the date of their last on-study assessment. Time to treatment failure was analyzed using Kaplan-Meier methods.

  • Time to Disease Relapse Following Surgical Intervention [ Time Frame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    Calculated only for those participants who underwent surgical intervention, and defined as the time from the date of first post-intervention radiographic disease assessment to the date of first observed PD. Participants with no post-intervention disease assessment had their time to relapse set to zero and censored in the analysis. Participants that had evidence of progression / recurrence at their first post-intervention disease assessment had a time to relapse of zero. For participants who had not progressed by the analysis data cut-off date, time to relapse was censored at the date of their last evaluable disease assessment. Time to relapse was analyzed using Kaplan-Meier metjhods.

  • Resection Rate [ Time Frame: From enrollment until the data cut-off date of 18 June 2009; median follow-up time was 34 weeks. ] [ Designated as safety issue: No ]
    The percentage of participants who underwent a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.


Enrollment: 154
Study Start Date: May 2007
Study Completion Date: June 2012
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panitumumab plus FOLFIRI
Participants received 6 mg/kg panitumumab intravenously (IV) once every 14 days in combination with FOLFIRI chemotherapy regimen consisting of irinotecan, infusional 5-fluorouracil, and leucovorin, until diagnosed with radiographic disease progression.
Drug: Panitumumab
Administered by intravenous infusion
Other Name: Vectibix
Drug: FOLFIRI
FOLFIRI chemotherapy was initiated on Day 1 of each treatment cycle at the following starting doses: irinotecan 180 mg/m², leucovorin 400 mg/m², 5-fluorouracil bolus 400 mg/m², 5-fluorouracil infusion 2400 mg/m².

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with histologically- or cytologically-confirmed metastatic adenocarcinoma of the colon and/or rectum.
  • Measurable disease according to modified RECIST guidelines.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Paraffin-embedded tissue or unstained tumour slides from primary or metastatic tumour available for central lab analysis.
  • Adequate haematologic, renal, hepatic and metabolic function.

Exclusion Criteria:

  • Central nervous system metastases.
  • Prior systemic therapy for the treatment of metastatic colorectal carcinoma with the exception of adjuvant fluoropyrimidine-based chemotherapy given at least six months prior to initiating study treatment.
  • Prior anti-epidermal growth factor receptor (EGFr) antibody therapy (e.g. cetuximab) or treatment with small molecule EGFr tyrosine kinase inhibitors (e.g. erlotinib).
  • Prior radiotherapy within 14 days prior to screening, and for which all signs of early radiological toxicity have not abated.
  • Significant cardiovascular disease including unstable angina or myocardial infarction within six months before initiating study treatment or a history of ventricular arrhythmia.
  • History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computed tomography (CT scan.
  • Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as > 4 loose stools per day).
  • History of Gilbert's syndrome or dihydropyrimidine deficiency.
  • Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection.
  • Any investigational agent within 30 days before initiation of study treatment.
  • Must not have had a major surgical procedure within 28 days prior to initiation of study treatment.
  • Subject who is pregnant or breast-feeding.
  • Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the course of the study and for six months after the last study drug administration for women, and one month for men.

    • Other protocol specified criteria and specific details may apply.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00508404

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

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00508404     History of Changes
Other Study ID Numbers: 20060314  EUDRACT Number 2006-006739-36 
Study First Received: July 26, 2007
Results First Received: December 18, 2015
Last Updated: December 18, 2015
Health Authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Sweden: Medical Products Agency
Belgium: Federal Agency for Medicines and Helath Products (FAMHP)

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
Irinotecan
Antibodies, Monoclonal
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2016