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

NCT ID: NCT01328171

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2022-01-31

Brief Summary

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

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A (FOLFOXIRI + Panitumumab)

FOLFOXIRI + Panitumumab

Group Type: EXPERIMENTAL

FOLFOXIRI + Panitumumab

Intervention Type: DRUG

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

B (FOLFOXIRI)

FOLFOXIRI

Group Type: ACTIVE_COMPARATOR

FOLFOXIRI

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Vectibix (Panitumumab); folic acid; 5-FU; oxaliplatin; irinotecan; folic acid; 5-FU; oxaliplatin; irinotecan

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

ClinAssess GmbH

INDUSTRY

Sponsor Role: collaborator

AIO-Studien-gGmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Geißler, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology and Gastroenterology, Academic Teaching Hospital Esslingen

Locations

Klinikum Esslingen

Esslingen am Neckar, Baden-Wurttemberg, Germany

SLK-Kliniken Heilbronn GmbH

Heilbronn, Baden-Wurttemberg, Germany

Ortenau Klinikum

Lahr, Baden-Wurttemberg, Germany

Klinikum Ludwigsburg

Ludwigsburg, Baden-Wurttemberg, Germany

Universitätsklinikum Mannheim

Mannheim, Baden-Wurttemberg, Germany

Klinikum Schwäbisch Gmünd

Mutlangen, Baden-Wurttemberg, Germany

Kreiskliniken Esslingen gGmbH Klinik Nürtingen

Nürtingen, Baden-Wurttemberg, Germany

Schwerpunktpraxis und Tagesklinik Onkologie Hämatologie Gastroenterologie Palliativmedizin Drs. Höring, Respondek, Schwinger, Thunert

Stuttgart, Baden-Wurttemberg, Germany

Universitätsklinikum Ulm Zentrum für Innere Medizin

Ulm, Baden-Wurttemberg, Germany

Klinikum Augsburg

Augsburg, Bavaria, Germany

Leopoldina-Krankenhaus der Stadt Schweinfurth gGmbH

Schweinfurt, Bavaria, Germany

Klinikum der J.W. Goethe-Universität Frankfurt

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Gießen und Marburg GmbH

Marburg, Hesse, Germany

Franziskus Hospital Niels-Stensen-Kliniken Klinik für Internistische Onkologie und Hämatologie

Georgsmarienhütte, Lower Saxony, Germany

Marienhospital Osnabrück Niels-Stensen-Kliniken Klinik für Innere Medizin

Osnabrück, Lower Saxony, Germany

St. Vincenz-Krankenhaus

Paderborn, North Rhine-Westphalia, Germany

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, Rhineland-Palatinate, Germany

Universitätsklinikum Halle

Halle, Saxony-Anhalt, Germany

Universitätsklinikum Jena

Jena, Thuringia, Germany

Countries

Germany

References

Modest DP, Martens UM, Riera-Knorrenschild J, Greeve J, Florschutz A, Wessendorf S, Ettrich T, Kanzler S, Norenberg D, Ricke J, Seidensticker M, Held S, Buechner-Steudel P, Atzpodien J, Heinemann V, Seufferlein T, Tannapfel A, Reinacher-Schick AC, Geissler M. FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). J Clin Oncol. 2019 Dec 10;37(35):3401-3411. doi: 10.1200/JCO.19.01340. Epub 2019 Oct 14.

Reference Type: DERIVED

PMID: 31609637 (View on PubMed)

Related Links

http://www.aio-portal.de

AIO-Homepage

Other Identifiers

2009-017731-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AIO KRK 0109

Identifier Type: -

Identifier Source: org_study_id