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Metastatic Colorectal CancerPhase 2VOLFINCT01328171

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

A Phase 2 study testing FOLFOXIRI + Panitumumab and FOLFOXIRI in people with Metastatic Colorectal Cancer, run by AIO-Studien-gGmbH at 19 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
FOLFOXIRI + Panitumumab and FOLFOXIRI
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
19 sitesGermany
Study dates
Apr 2011to Jan 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

Germany19 sites

  • Klinikum Augsburg

    Augsburg, Bavaria, 86156

  • Klinikum Esslingen

    Esslingen am Neckar, Baden-Wurttemberg, 73730

  • Klinikum der J.W. Goethe-Universität Frankfurt

    Frankfurt am Main, Hesse, 60590

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

    Georgsmarienhütte, Lower Saxony, 49124

  • Universitätsklinikum Halle

    Halle, Saxony-Anhalt, 6120

  • SLK-Kliniken Heilbronn GmbH

    Heilbronn, Baden-Wurttemberg, 74078

  • Universitätsklinikum Jena

    Jena, Thuringia, 7740

  • Ortenau Klinikum

    Lahr, Baden-Wurttemberg, 77933

  • Klinikum Ludwigsburg

    Ludwigsburg, Baden-Wurttemberg, 71640

  • Universitätsklinikum Mannheim

    Mannheim, Baden-Wurttemberg, 68135

  • Universitätsklinikum Gießen und Marburg GmbH

    Marburg, Hesse, 35043

  • Klinikum Schwäbisch Gmünd

    Mutlangen, Baden-Wurttemberg, 73557

  • Kreiskliniken Esslingen gGmbH Klinik Nürtingen

    Nürtingen, Baden-Wurttemberg, 72622

  • Marienhospital Osnabrück Niels-Stensen-Kliniken Klinik für Innere Medizin

    Osnabrück, Lower Saxony, 49074

  • St. Vincenz-Krankenhaus

    Paderborn, North Rhine-Westphalia, 33098

  • Leopoldina-Krankenhaus der Stadt Schweinfurth gGmbH

    Schweinfurt, Bavaria, 97422

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

    Stuttgart, Baden-Wurttemberg, 70190

  • Klinikum Mutterhaus der Borromäerinnen gGmbH

    Trier, Rhineland-Palatinate, 54290

  • Universitätsklinikum Ulm Zentrum für Innere Medizin

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

About this study

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

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

Being tested
FOLFOXIRI + Panitumumab, FOLFOXIRI
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFOXIRI + PanitumumabDrug

    Also called Vectibix (Panitumumab), folic acid, 5-FU, oxaliplatin

    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

  • FOLFOXIRIDrug

    Also called folic acid, 5-FU, oxaliplatin, irinotecan

    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

Study groups in NCT01328171
Study groupRoleWhat they receive
A (FOLFOXIRI + Panitumumab)ExperimentalFOLFOXIRI + Panitumumab
Receives: Drug: FOLFOXIRI + Panitumumab
B (FOLFOXIRI)Active comparatorFOLFOXIRI
Receives: Drug: FOLFOXIRI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. overall response rate

    RECIST

    Measured: up to about 6 month

Secondary outcomes (13)

  1. overall response rate in each cohort

    RECIST

    Measured: up to about 6 month

  2. secondary resection rate with curative intent for patients cohort I

    Measured: up to about 6 month

  3. pathological response in liver surgery specimen

    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

    Measured: up to about 6 month

  4. disease control rate

    CR + PR + SD rate according to RECIST

    Measured: up to about 6 month

  5. progression free survival

    Measured: 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

  6. duration of response

    analyzed for responders only

    Measured: 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

  7. time to response

    Measured: up to about 6 month

  8. overall survival

    Measured: From date of randomization until the date of death from any cause assessed up to 4 years

  9. time to recurrence (cohort II in case of secondary resection)

    Measured: up to 4 years

  10. toxicity and feasibility

    number of patients with adverse events and severity according to NCI CTC 3.0

    Measured: up to about 6 month

  11. liver toxicity for resected patients (central histological review); biopsies should be obtained for all patients pre-treatment

    histological findings according to CASH/SOS scores

    Measured: up to 1 year

  12. QL (QLQ C30)

    scores according to EORTC QLQ-C30 scoring manual (Quality of life)

    Measured: Pre-treatment, before start of every 3rd cycle and at the end of treatment

  13. translational research (EGFR genetics and proteomics): prognostic and predictive impact on efficacy outcomes

    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

    Measured: up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Apr 2011 (estimated)
  2. Study startApr 2011
  3. Primary completionJun 2017
  4. Study completionJan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01328171
Sponsor's protocol ID
AIO KRK 0109
Other IDs
2009-017731-17, 2009
Acronym
VOLFI
Status last verified
Jun 2023
First submitted
30 Mar 2011
Last updated
15 Jun 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • Klingler TM, Martens UM, Riera-Knorrenschild J, Wessendorf S, Ettrich T, Kanzler S, Lugani S, Rohleder E, Stahler A, Hasenburg AA, Held S, Buechner-Steudel P, Atzpodien J, Heinemann V, Geissler M, Modest DP, Werner J. Quality of life in patients with RAS wild-type metastatic colorectal cancer treated mFOLFOXIRI + panitumumab versus FOLFOXIRI: A prespecified secondary analysis of the phase II VOLFI AIO-KRK 0109 trial. Eur J Cancer. 2026 Sep 11;247:117045. doi: 10.1016/j.ejca.2026.117045. Online ahead of print.

    PubMed 42743885

  • 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.

    PubMed 31609637

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FOLFOXIRI + Panitumumab and FOLFOXIRI in people with Metastatic Colorectal Cancer, run by AIO-Studien-gGmbH at 19 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

overall response rate (time frame: up to about 6 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01328171, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2023.

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