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

NCT01328171 | Completed Phase 2 DMC

• 2 other identifiers: AIO KRK 01092009-017731-17
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 19

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

Outcome Measures

Primary Outcomes (1)

• overall response rate

  RECIST

  up to about 6 month

Secondary Outcomes (13)

• overall response rate in each cohort

  up to about 6 month

• secondary resection rate with curative intent for patients cohort I

  up to about 6 month

• pathological response in liver surgery specimen

  up to about 6 month

• disease control rate

  up to about 6 month

• progression free survival

  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

Study Arms (2)

A (FOLFOXIRI + Panitumumab)

EXPERIMENTAL

FOLFOXIRI + Panitumumab

Drug: FOLFOXIRI + Panitumumab

B (FOLFOXIRI)

ACTIVE COMPARATOR

FOLFOXIRI

Drug: FOLFOXIRI

Interventions

FOLFOXIRI + Panitumumab 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

Also known as: Vectibix (Panitumumab), folic acid, 5-FU, oxaliplatin, irinotecan

A (FOLFOXIRI + Panitumumab)

FOLFOXIRI 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

Also known as: folic acid, 5-FU, oxaliplatin, irinotecan

B (FOLFOXIRI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Amgen: collaborator
• ClinAssess GmbH: collaborator

Study Sites (19)

Klinikum Esslingen

Esslingen am Neckar, Baden-Wurttemberg, 73730, Germany

Location

SLK-Kliniken Heilbronn GmbH

Heilbronn, Baden-Wurttemberg, 74078, Germany

Location

Ortenau Klinikum

Lahr, Baden-Wurttemberg, 77933, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, Baden-Wurttemberg, 71640, Germany

Location

Universitätsklinikum Mannheim

Mannheim, Baden-Wurttemberg, 68135, Germany

Location

Klinikum Schwäbisch Gmünd

Mutlangen, Baden-Wurttemberg, 73557, Germany

Location

Kreiskliniken Esslingen gGmbH Klinik Nürtingen

Nürtingen, Baden-Wurttemberg, 72622, Germany

Location

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

Stuttgart, Baden-Wurttemberg, 70190, Germany

Location

Universitätsklinikum Ulm Zentrum für Innere Medizin

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum Augsburg

Augsburg, Bavaria, 86156, Germany

Location

Leopoldina-Krankenhaus der Stadt Schweinfurth gGmbH

Schweinfurt, Bavaria, 97422, Germany

Location

Klinikum der J.W. Goethe-Universität Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Marburg, Hesse, 35043, Germany

Location

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

Georgsmarienhütte, Lower Saxony, 49124, Germany

Location

Marienhospital Osnabrück Niels-Stensen-Kliniken Klinik für Innere Medizin

Osnabrück, Lower Saxony, 49074, Germany

Location

St. Vincenz-Krankenhaus

Paderborn, North Rhine-Westphalia, 33098, Germany

Location

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, Rhineland-Palatinate, 54290, Germany

Location

Universitätsklinikum Halle

Halle, Saxony-Anhalt, 6120, Germany

Location

Universitätsklinikum Jena

Jena, Thuringia, 7740, Germany

Location

Related Publications (1)

• 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.

  PMID: 31609637 DERIVED

Related Links

• AIO-Homepage

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Folic Acid; Fluorouracil; Oxaliplatin; Irinotecan; FOLFOXIRI protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids

Study Officials

• Michael Geißler, MD, PhD

  Department of Oncology and Gastroenterology, Academic Teaching Hospital Esslingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 4, 2011
• Study Start: April 1, 2011
• Primary Completion: June 1, 2017
• Study Completion: January 1, 2022
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

DE (19)