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    Summary
    EudraCT Number:2008-004752-77
    Sponsor's Protocol Code Number:20070820
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-06-30
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2008-004752-77
    A.3Full title of the trial
    A Phase 2 Study of Panitumumab Plus Irinotecan Followed by Panitumumab Plus AMG 479 in Subjects With Metastatic Colorectal Carcinoma Expressing Wild Type KRAS and Refractory to Oxaliplatin- or Irinotecan- and Oxaliplatin-containing Regimens to Evaluate Mechanisms of Acquired Resistance to Panitumumab
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Ph2 Biomarker (Mechanism of K-ras Dependency) in Wt KRAS Metastatic Colorectal Cancer Patients
    A.4.1Sponsor's protocol code number20070820
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT00891930
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAmgen Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAmgen Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen (EUROPE) GmbH
    B.5.2Functional name of contact pointIHQ Medical Information – Clinical
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZug
    B.5.3.3Post code(CH-)6300
    B.5.3.4CountrySwitzerland
    B.5.6E-mailMedinfoInternational@amgen.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Vectibix 20mg/ml concentrate for solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePanitumumab
    D.3.2Product code AMG 954
    D.3.4Pharmaceutical form Concentrate and solvent for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPanitumumab
    D.3.9.1CAS number 339177-26-3
    D.3.9.2Current sponsor codeAMG 954
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typefully human IgG2 monoclonal antibody
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAMG 479
    D.3.2Product code AMG 479
    D.3.4Pharmaceutical form Concentrate and solvent for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGanitumab
    D.3.9.2Current sponsor codeAMG 479
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number14
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic colorectal cancer
    E.1.1.1Medical condition in easily understood language
    Metastatic Colorectal Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 15.1
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part 1:
    To determine if acquired resistance to panitumumab therapy in subjects with KRAS wildtype mCRC correlates with emergence of mutant KRAS tumors. (Acquired resistance is defined as disease progression on panitumumab and irinotecan that occurs after a period of disease response or stable disease on treatment with this regimen is observed and radiographically-confirmed.)
    Part 2:
    To determine if inhibition of the IGF-1R pathway with AMG 479 can overcome resistance to panitumumab therapy, as demonstrated by the objective response rate (ORR) to panitumumab and AMG 479 following disease progression on panitumumab and irinotecan.
    E.2.2Secondary objectives of the trial
    Part 1:
    To determine ORR and other measures of efficacy (ie, TTR, DOR, PFS, OS) to panitumumab plus irinotecan
    To evaluate the safety of panitumumab and irinotecan
    Part 2:
    To determine measures of efficacy (ie, TTR, DOR, PFS, OS) of panitumumab plus AMG 479
    To evaluate the safety of panitumumab and AMG 479
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum
    • Wild-type KRAS tumor status of archival tumor tissue (preferably from the primary tumor) confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method
    • Radiographic evidence of disease progression while on or ≤ 6 months after treatment with irinotecan- and oxaliplatin- or oxaliplatin-based chemotherapy for mCRC
    • Subjects in whom relapse is diagnosed within 6 months after completing adjuvant chemotherapy (with oxaliplatin-containing regimen) will be considered as having failed a prior regimen for metastatic disease.
    • Radiographic measurement of tumor burden done within 28 days prior to Day 1 (start of treatment with investigational product)
    • At least 1 uni-dimensionally measurable lesion ≥ 20 mm using conventional CT or MRI or ≥ 10 mm by spiral CT per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated
    • At least 1 tumor (metastatic lesion or unresected primary tumor) that is amenable to core needle biopsy, as determined by the clinician who will perform the biopsy
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix E)
    • Male or female ≥ 18 years of age at the time of informed consent
    • Willing to undergo two core biopsy procedures of tumors (metastasis or unresected primary)
    E.4Principal exclusion criteria
    • History of prior or concurrent central nervous system (CNS) metastases
    • Prior treatment with anti-EGFR antibodies (eg, panitumumab, cetuximab) or EGFR small molecule inhibitors (eg, erlotinib, gefitinib)
    • Prior treatment with monoclonal antibodies directed against IGF-1R or small molecule inhibitors directed against IGF-1R
    • Use of systemic chemotherapy and radiotherapy ≤ 21 days before enrollment Subject must have recovered from acute toxicities related to radiotherapy.
    • Use of any antibody therapy (eg, bevacizumab) ≤ 42 days before enrollment
    • Use of anti-tumor therapies including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment
    • Known UGT1A1 polymorphisms predisposing to increased irinotecan toxicity
    • History of irinotecan intolerance that may interfere with planned treatment
    • History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan
    • Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection
    • Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion)
    • Any uncontrolled concurrent illness (eg, infection, bleeding diathesis) or history of any medical condition that may interfere with the interpretation of the study results
    • Major surgical procedure ≤ 28 days before enrollment or minor surgical procedure ≤ 14 days before enrollment. Subjects must have recovered from surgery related toxicities. Core biopsy, central venous catheter placement, fine needle aspiration, thoracentesis, or paracentesis is not considered a major or minor surgical procedure.
    E.5 End points
    E.5.1Primary end point(s)
    Emergence of Mutant KRAS: KRAS mutation status changed from wild-type at baseline to mutant at the time of the second biopsy following the radiographic evidence of acquired resistance to panitumumab plus irinotecan (Part 1).

    Objective Response Rate (ORR): Confirmed complete or partial response (per modified RECIST) to panitumumab and AMG 479 (Part 2)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part 1 - at the time of the second biopsy
    Part 2- The incidences of either a confirmed complete response (CR) or partial response (PR) per modified RECIST criteria v1.0 during the treatment of regimen 2. A confirmed CR requires 2 assessments of CR at least 28 days apart. A confirmed PR requires 2 assessments at least 28 days apart of CR or PR. All subjects that do not meet the criteria for a confirmed CR or PR by the analysis cut-off date will be considered non-responders.
    E.5.2Secondary end point(s)
    Efficacy: ORR (Part 1), Time to Response (TTR), Duration of Response (DOR), Progression free Survival (PFS), On-treatment PFS, and Overall Survival (OS) (both Part 1 and Part 2)
    • Safety: Incidence and severity of adverse events, significant changes in laboratory values, incidence of anti-antibody formation (both Part 1 and Part 2)

    Objective Response Rate (ORR) in Part 1: The incidences of either a confirmed complete response (CR) or partial response (PR) per modified RECIST criteria v1.0 during the treatment of regimen 1. A confirmed CR requires 2 assessments of CR at least 28 days apart. A confirmed PR requires 2 assessments at least 28 days apart of CR or PR. All subjects that do not meet the criteria for a confirmed CR or PR by the analysis cut-off date will be considered non-responders.
    • Progression-free survival (PFS): Time from the first dose of investigational product to the first date of disease progression per the modified RECIST criteria v1.0 or death prior to the earlier of the analysis data cutoff date, initiating a new line of anti-tumor therapy, and receiving study treatment in Part 2 where applicable.
    Subjects who have not progressed or died by the analysis cutoff date will be censored at their last evaluable disease assessment date
    • Overall survival (OS): Time from the first dose of investigational product to the date of death in both Part 1 and Part 2. Subjects who have not died by the analysis cutoff date will be censored at their last contact date.
    • Time to Response (TTR): Time from the first dose of the investigational product to the date of first confirmed objective response in both Part 1 and Part 2. Calculated only for those subjects with a confirmed objective response.
    • Duration of response (DOR): Time from the first confirmed objective response to disease progression per the modified RECIST criteria v1.0 in both Part 1 and Part 2.
    Subjects not meeting criteria for progression by the analysis cutoff date will be censored at their last evaluable disease assessment date. Calculated only for subjects with a confirmed objective response.
    Safety in both Part 1 and Part 2 will include, but not be limited to, the following:
    • Incidence and severity of adverse events
    • Significant changes in laboratory values
    • Incidence of anti-antibody formation
    E.5.2.1Timepoint(s) of evaluation of this end point
    As described for each secondary endpoint above
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study will occur when all subjects have completed or have had the opportunity to complete the 30-day safety follow-up visit or 2 years (± 2 months) after the last subject is enrolled in Part 1, whichever is later.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 38
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 37
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state7
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 75
    F.4.2.2In the whole clinical trial 75
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Expected normal treatment
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2009-07-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-07-23
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-07-30
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