FOLFOXIRI With or Without Panitumumab in Metastatic Colorectal Cancer (VOLFI)

This study is currently recruiting participants.
Verified September 2013 by AIO-Studien-gGmbH
Sponsor:
Collaborators:
Amgen
ClinAssess GmbH
Information provided by (Responsible Party):
AIO-Studien-gGmbH
ClinicalTrials.gov Identifier:
NCT01328171
First received: March 30, 2011
Last updated: April 8, 2014
Last verified: September 2013
  Purpose

The aim of the trial is to optimize response rates and rates of secondary resections of metastases in patients with initially non-resectable metastatic colorectal cancer of RAS wildtype. The patients will be treated in two therapy groups:

Experimental arm A: Chemotherapy with FOLFOXIRI + panitumumab Standard arm B: Chemotherapy with FOLFOXIRI


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: FOLFOXIRI + Panitumumab
Drug: FOLFOXIRI
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AIO-Studien-gGmbH:

Primary Outcome Measures:
  • overall response rate [ Time Frame: up to about 6 month ] [ Designated as safety issue: No ]
    RECIST


Secondary Outcome Measures:
  • overall response rate in each cohort [ Time Frame: up to about 6 month ] [ Designated as safety issue: No ]
    RECIST

  • secondary resection rate with curative intent for patients cohort I [ Time Frame: up to about 6 month ] [ Designated as safety issue: No ]
  • pathological response in liver surgery specimen [ Time Frame: up to about 6 month ] [ Designated as safety issue: No ]
    metrics: Pathological complete response (pCR): no residual cancer cells;major response (pPR): 1% to 49% residual cancer cells remaining; minor response (pMR): 50% to 99% residual cancer cells remaining; no response (pNR): 100% residual cancer cells remaining

  • disease control rate [ Time Frame: up to about 6 month ] [ Designated as safety issue: No ]
    CR + PR + SD rate according to RECIST

  • progression free survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years ] [ Designated as safety issue: No ]
  • duration of response [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years ] [ Designated as safety issue: No ]
    analyzed for responders only

  • time to response [ Time Frame: up to about 6 month ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: From date of randomization until the date of death from any cause assessed up to 4 years ] [ Designated as safety issue: No ]
  • time to recurrence (cohort II in case of secondary resection) [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • toxicity and feasibility [ Time Frame: up to about 6 month ] [ Designated as safety issue: Yes ]
    number of patients with adverse events and severity according to NCI CTC 3.0

  • liver toxicity for resected patients (central histological review); biopsies should be obtained for all patients pre-treatment [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    histological findings according to CASH/SOS scores

  • QL (QLQ C30) [ Time Frame: Pre-treatment, before start of every 3rd cycle and at the end of treatment ] [ Designated as safety issue: No ]
    scores according to EORTC QLQ-C30 scoring manual (Quality of life)

  • translational research (EGFR genetics and proteomics): prognostic and predictive impact on efficacy outcomes [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    Determination of EGFR mutations (exons 18, 19, 20, 21) in tumor tissue; determination of PIK3CA mutations (exon 9, 20) in tumor tissue; determination of EGFR, ERCC1, TS, MTHFR, OPRT, DHFR and CDKN polymorphism from normal and tumor tissue; determination of ERCC1, PTEN and TS protein expression in tumor tissue; epigenetic candidates; further exploratory studies such as miRNA analysis as approved by the AIO review board


Estimated Enrollment: 93
Study Start Date: April 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A (FOLFOXIRI + Panitumumab)
FOLFOXIRI + Panitumumab
Drug: FOLFOXIRI + Panitumumab
irinotecan 150 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 3000 mg/m² cont. inf. + panitumumab, iv, 6 mg/kg BW all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles
Other Names:
  • Vectibix (Panitumumab)
  • folic acid
  • 5-FU
  • oxaliplatin
  • irinotecan
Active Comparator: B (FOLFOXIRI)
FOLFOXIRI
Drug: FOLFOXIRI
irinotecan 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 3200 mg/m² cont. inf. all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles
Other Names:
  • folic acid
  • 5-FU
  • oxaliplatin
  • irinotecan

  Eligibility

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

Inclusion Criteria:

  • 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
  • Cohort II: Chance of secondary resection with curative intent defined and reviewed by expert panel
  • Adult patients (≥ 18 years of age)
  • 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)
  • Performance status ECOG 0-1
  • Male and female subjects > 18 years of age
  • 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.

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 enrolment.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01328171

Contacts
Contact: Michael Geißler, MD, PhD 0049 711 3103 ext 2451 m.geissler@klinikum-esslingen.de

Locations
Germany
Klinikum Esslingen Recruiting
Esslingen, Baden-Württemberg, Germany, 73730
Contact: Michael Geißler, Prof. Dr.    0049 - 711 - 31 03 ext 24 51    m.geissler@klinikum-esslingen.de   
Principal Investigator: Michael Geißler, Prof. Dr.         
Sub-Investigator: Heike Mönnich, Dr. med.         
Sub-Investigator: Jochen Bauer, Dr. med.         
Sub-Investigator: Sven Weßendorf, Dr. med.         
Sub-Investigator: Carsten Schwänen, Dr. med.         
SLK-Kliniken Heilbronn GmbH Recruiting
Heilbronn, Baden-Württemberg, Germany, 74078
Contact: Uwe Martens, Prof. Dr.    0049 - 7131 - 49 28 ext 01    uwe.martens@slk-kliniken.de   
Principal Investigator: Uwe Martens, Prof. Dr.         
Sub-Investigator: Stefanie Gabat, Dr.         
Sub-Investigator: Marlene Weiß, Dr.         
Sub-Investigator: Markus Lindauer, Dr.         
Sub-Investigator: Josef Huber         
Ortenau Klinikum Recruiting
Lahr, Baden-Württemberg, Germany, 77933
Contact: Matthias Egger, Dr.    0049 - 07821 - 93 ext 24 00    Matthias.Egger@le.ortenau-klinikum.de   
Principal Investigator: Matthias Egger, Dr.         
Sub-Investigator: Leonhard Mohr, Prof. Dr.         
Sub-Investigator: Alexander Voelkel         
Klinikum Ludwigsburg Active, not recruiting
Ludwigsburg, Baden-Württemberg, Germany, 71640
Universitätsklinikum Mannheim Active, not recruiting
Mannheim, Baden-Württemberg, Germany, 68135
Klinikum Schwäbisch Gmünd Recruiting
Mutlangen, Baden-Württemberg, Germany, 73557
Contact: Holger Hebart, Prof. Dr.    0049 - 71 71 - 701 13 ext 02    holger.hebart@Stauferklinikum.de   
Principal Investigator: Holger Hebart, Prof. Dr.         
Kreiskliniken Esslingen gGmbH Klinik Nürtingen Active, not recruiting
Nürtingen, Baden-Württemberg, Germany, 72622
Schwerpunktpraxis und Tagesklinik Onkologie Hämatologie Gastroenterologie Palliativmedizin Drs. Höring, Respondek, Schwinger, Thunert Active, not recruiting
Stuttgart, Baden-Württemberg, Germany, 70190
Universitätsklinikum Ulm Zentrum für Innere Medizin Recruiting
Ulm, Baden-Württemberg, Germany, 89081
Contact: Thomas Ettrich, Dr.    0049 - 0731 - 500 - 445 ext 08    thomas.ettrich@uniklinik-ulm.de   
Principal Investigator: Thomas Ettrich, Dr.         
Klinikum Augsburg Active, not recruiting
Augsburg, Bayern, Germany, 86156
Leopoldina-Krankenhaus der Stadt Schweinfurth gGmbH Recruiting
Schweinfurt, Bayern, Germany, 97422
Contact: Stephan Kanzler, PD Dr.    0049 - 09721 - 720 24 ext 82    akram@leopoldina.de   
Principal Investigator: Stephan Kanzler, PD Dr.         
Sub-Investigator: Hans Reinel, Dr. med.         
Sub-Investigator: Andrea Buwe         
Klinikum der J.W. Goethe-Universität Frankfurt Recruiting
Frankfurt, Hessen, Germany, 60590
Contact: Lothar Bergmann, Prof. Dr.    0049 - 69 - 63 01 ext 51 21    L.Bergmann@em.uni-frankfurt.de   
Principal Investigator: Lothar Bergmann, Prof. Dr.         
Sub-Investigator: Valeska Möntenich, Dr.         
Sub-Investigator: Luise Mauze, Dr.         
Universitätsklinikum Gießen und Marburg GmbH Recruiting
Marburg, Hessen, Germany, 35043
Contact: Jorge Riera Knorrenschild, Dr.    0049 - 6421 - 286 ext 2784    rierakno@med.uni-marburg.de   
Principal Investigator: Jorge Riera Knorrenschild, Dr.         
Sub-Investigator: Manela Jänike         
Franziskus Hospital Niels-Stensen-Kliniken Klinik für Internistische Onkologie und Hämatologie Recruiting
Georgsmarienhütte, Niedersachsen, Germany, 49124
Contact: Jens Atzpodien, Prof. Dr.    0049 541 502 ext 24 60    atzpodien@franziskus.com   
Marienhospital Osnabrück Niels-Stensen-Kliniken Klinik für Innere Medizin Active, not recruiting
Osnabrück, Niedersachsen, Germany, 49074
St. Vincenz-Krankenhaus Active, not recruiting
Paderborn, Nordrhein-Westfalen, Germany, 33098
Klinikum Mutterhaus der Borromäerinnen gGmbH Recruiting
Trier, Rheinland-Pfalz, Germany, 54290
Contact: Michael R. Clemens, Prof. Dr.    0049 - 651 - 947 ext 23 77    clemens@mutterhaus.de   
Principal Investigator: Michael R. Clemens, Prof. Dr.         
Sub-Investigator: Rolf Mahlberg, Dr. med.         
Sub-Investigator: Boris Meuter, Dr. med.         
Universitätsklinikum Halle Recruiting
Halle, Sachsen-Anhalt, Germany, 6120
Contact: Petra Büchner-Steudel, Dr.    0049 - 345 - 557 ext 26 68    petra.buechner-steudel@medizin.uni-halle.de   
Principal Investigator: Petra Büchner-Steudel, Dr.         
Sub-Investigator: Philipp Thermann, Dr. med.         
Sub-Investigator: Alexander Stein, Dr. med.         
Sub-Investigator: Sonja Hiemer         
Universitätsklinikum Jena Recruiting
Jena, Thüringen, Germany, 7740
Contact: Udo Lindig, Dr. med.    0049 3641 - 9 32 ext 45 86    udo.lindig@med.uni-jena.de   
Principal Investigator: Udo Lindig, Dr. med.         
Sub-Investigator: Lars-Olof Mügge, Dr. med.         
Sub-Investigator: Ekkehard Eigendorff, Dr. med.         
Sub-Investigator: Frank Pesters         
Sponsors and Collaborators
AIO-Studien-gGmbH
Amgen
ClinAssess GmbH
Investigators
Principal Investigator: Michael Geißler, MD, PhD Department of Oncology and Gastroenterology, Academic Teaching Hospital Esslingen
  More Information

Additional Information:
No publications provided

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT01328171     History of Changes
Other Study ID Numbers: AIO KRK 0109, 2009-017731-17
Study First Received: March 30, 2011
Last Updated: April 8, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

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
Folic Acid
Vitamin B Complex
Oxaliplatin
Irinotecan
Antibodies, Monoclonal
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014