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    Summary
    EudraCT Number:2009-017731-17
    Sponsor's Protocol Code Number:AIO-KRK-0109
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2010-10-29
    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 ConcernedGermany - PEI
    A.2EudraCT number2009-017731-17
    A.3Full title of the trial
    An open-label 2:1 randomized phase II study of panitumumab plus FOLFOXIRI or FOLFOXIRI alone as first-line treatment of patients with non-resectable metastatic colorectal cancer and RAS wild-type
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    FOLFOXIRI with or without panitumumab in metastatic colorectal cancer
    A.3.2Name or abbreviated title of the trial where available
    VOLFI
    A.4.1Sponsor's protocol code numberAIO-KRK-0109
    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 SponsorAIO-Studien-gGmbh
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAmgen GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClin Assess GmbH
    B.5.2Functional name of contact pointCRO
    B.5.3 Address:
    B.5.3.1Street AddressBirkenbergstr. 82
    B.5.3.2Town/ cityLeverkusen
    B.5.3.3Post code51379
    B.5.3.4CountryGermany
    B.5.4Telephone number004902171363360
    B.5.5Fax number0049021713633655
    B.5.6E-mailinfo@clinassess.de
    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
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V.
    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.3.4Pharmaceutical form Concentrate 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.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 typeEGFR-targeted monoclonal antibody
    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
    non-resectable metastatic colorectal cancer
    E.1.1.1Medical condition in easily understood language
    non-resectable 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 20.0
    E.1.2Level LLT
    E.1.2Classification code 10010036
    E.1.2Term Colorectal carcinoma
    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
    To assess efficacy (objective response rate, ORR) of adding panitumumab to FOLFOXIRI in patients with newly diagnosed metastatic colorectal cancer expressing wild-type RAS
    Cohort I) Definitively unresectable metastatic disease, with a focus on symptomatic metastatic disease and/or large tumor load,
    or
    Cohort II) With chance of secondary resection with curative intent
    according to recent S3 guidelines of the German Cancer Society. The ORR will be compared to expectations derived from historical data, which are verified by a randomised control group without the antibody.
    E.2.2Secondary objectives of the trial
    • To evaluate ORR in both cohorts
    • To evaluate secondary resection rate with curative intent for patients cohort II
    • To evaluate pathological response in liver surgery specimen (pretreatment biopsy of liver metastases in cohort II within the translational research program)
    • To evaluate disease control rate (DCR)
    • To evaluate progression-free survival (PFS)
    • To evaluate duration of response
    • To evaluate time to response
    • To evaluate overall survival (OS)
    • To evaluate toxicity and feasibility
    • To assess time to recurrence (cohort II in case of secondary resection)
    • To assess liver toxicity, and histopathological response rate for resected patients (central histological review, cf. appendix 6)
    • To assess quality of life
    by adding panitumumab to FOLFOXIRI.
    • Translational research: detection of EGFR expression, functional genetic polymorphisms of the EGFR gene, EGFR amplification, EGFR activation, EGFR signalling, epigenetics (methylation) and miRNA profiles
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Adult patients (≥ 18 years of age)
    • Cohort I: Histologically confirmed and definitively inoperable or irresectable metastatic colorectal cancer. Focus on patients with large tumor load at metastatic sites and/or symptomatic metastatic disease or
    • Cohort II: Chance of secondary resection with curative intent defined and reviewed by expert panel
    • RAS wild-type tested in
    ▪ KRAS exon 2 (codons 12/13)
    ▪ KRAS exon 3 (codons 59/61)
    ▪ KRAS exon 4 (codons 117/146)
    ▪ NRAS exon 2 (codons 12/13)
    ▪ NRAS exon 3 (codons 59/61)
    ▪ NRAS exon 4 (codons 117/146)
    assessed by an institution participating in and certified by the specific working group of the Deutsche Gesellschaft für Pathologie)
    • At least one measurable lesion according to RECIST measured within 3 weeks prior to registration
    • No previous chemotherapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago) with exception of 1 application of FOLFOXIRI in patients with need of immediate treatment while waiting for the result of RAS mutation testing.
    • Performance status ECOG 0-1
    • Adequate haematological, hepatic, renal, and metabolic function parameters:
    Leukocytes > 3000/mm³, ANC ≥ 1500/mm3, platelets ≥ 100,000/mm3, Hb > 9g/dl (may be transfused or treated with erythropoietin to maintain or exceed this level)
    Creatinine clearance ≥ 50 ml/min or serum creatinine ≤ 1.5 x upper limit of normal
    Bilirubin ≤ 1.5 x upper limit of normal, GOT-GPT ≤ 2.5 x upper limit of normal in absence of liver metastases, or ≤ 5 x upper limit of normal in presence of liver metastases, AP ≤ 5 x upper limit of normal
    Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal (may be substituted to maintain or exceed this level)
    • Negative pregnancy test and willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
    • Before subject registration, written informed consent must be given according to ICH-GCP, and national/local regulations.
    E.4Principal exclusion criteria
    • Past or current history of malignancies except for the indication under this study and curatively treated:
    - Basal and squamous cell carcinoma of the skin
    - In-situ carcinoma of the cervix
    - Other malignant disease without recurrence after at least 5 years of follow-up
    • Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrollment.
    • Clinically relevant interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
    • History of evidence upon physical examination of CNS disease unless adequately treated (e.g. primary brain tumour, seizure not controlled with standard medical therapy, brain metastases or history of stroke).
    • Pre-existing neuropathy > grade 1 (NCI CTCAE), except for loss of tendon reflex
    • Allogeneic transplantation requiring immunosuppressive therapy.
    • Severe non-healing wounds, ulcers or bone fractions.
    • Evidence of bleeding diathesis or coagulopathy.
    • Patients not receiving therapeutic anticoagulation must have an INR < 1,5 ULN and aPTT > 1,5 ULN within 7 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of randomisation.
    • Concomitant therapy with certain anti-viral medicines (sorivudine and brivudine or analogue compounds).
    • Major surgical procedure, open biopsy, nor significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study except for surgery for colorectal cancer with curative intent and central venous line placement for chemotherapy administration.
    • Pregnancy or breastfeeding women.
    • Subjects with known allergy to the study drugs or to any of its excipients.
    • Known DPD deficiency.
    • Current or recent (within the 28 days prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
    • Known grade III/IV allergic reaction against monoclonal antibodies.
    • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the subject before registration in the trial.
    E.5 End points
    E.5.1Primary end point(s)
    Combined objective response rate for patient cohort I and II
    E.5.1.1Timepoint(s) of evaluation of this end point
    end of treatment
    E.5.2Secondary end point(s)
    • ORR in both cohorts
    • Secondary resection rate with curative intent for patients cohort II
    • Pathological response in liver surgery specimen (pretreatment biopsy of liver metastases in cohort II within the translational research program)
    • DCR
    • PFS
    • Duration of response
    • Time to response
    • OS
    • Time to recurrence (cohort II in case of secondary resection
    • Toxicity and feasibility
    • Liver toxicity and histopathological response rate for resected patients; biopsies both from healthy liver tissue and liver metastases should be obtained for all patients of cohort II (chance of secondary resection) pre-treatment
    • QL (QLQ C30)
    With respect of quality of life, the difference in the mean value of the global quality of life dimension of the EORTC QLQ C30 is assessed, calculated as the average of all available time points from 6 weeks to 24 weeks after randomization; the effect of palliative treatment on quality of life (treatment vs. baseline); evaluation of the prognostic impact of the quality of life and comparison to performance status; correlation between response rate and quality of life and between symptomatic/asymptomatic patients and quality of life.
    • Translational research: detection of EGFR expression, functional genetic polymorphisms of the EGFR gene, EGFR amplification, EGFR activation, EGFR signalling, epigenetics (methylation) and miRNA profiles
    E.5.2.1Timepoint(s) of evaluation of this end point
    end of trial
    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 Yes
    E.6.11Pharmacogenomic No
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Standard Background Treatment with FOLFOXIRI
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned40
    E.8.5The trial involves multiple Member States No
    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 Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    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 months6
    E.8.9.1In the Member State concerned days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 61
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 32
    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 state93
    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)
    cf. section 6.4 of the protocol
    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 Decision2011-01-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-02-01
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-01-20
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