Clinical Trials /

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

NCT01328171

Description:

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

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: FOLFOXIRI With or Without Panitumumab in Metastatic Colorectal Cancer (VOLFI)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: AIO KRK 0109
  • SECONDARY ID: 2009-017731-17
  • NCT ID: NCT01328171

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
FOLFOXIRI + PanitumumabVectibix (Panitumumab), folic acid, 5-FU, oxaliplatin, irinotecanA (FOLFOXIRI + Panitumumab)
FOLFOXIRIfolic acid, 5-FU, oxaliplatin, irinotecanB (FOLFOXIRI)

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

Trial Arms

NameTypeDescriptionInterventions
A (FOLFOXIRI + Panitumumab)ExperimentalFOLFOXIRI + Panitumumab
  • FOLFOXIRI + Panitumumab
B (FOLFOXIRI)Active ComparatorFOLFOXIRI
  • FOLFOXIRI

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:overall response rate
Time Frame:up to about 6 month
Safety Issue:
Description:RECIST

Secondary Outcome Measures

Measure:overall response rate in each cohort
Time Frame:up to about 6 month
Safety Issue:
Description:RECIST
Measure:secondary resection rate with curative intent for patients cohort I
Time Frame:up to about 6 month
Safety Issue:
Description:
Measure:pathological response in liver surgery specimen
Time Frame:up to about 6 month
Safety Issue:
Description: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
Measure:disease control rate
Time Frame:up to about 6 month
Safety Issue:
Description:CR + PR + SD rate according to RECIST
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:analyzed for responders only
Measure:time to response
Time Frame:up to about 6 month
Safety Issue:
Description:
Measure:overall survival
Time Frame:From date of randomization until the date of death from any cause assessed up to 4 years
Safety Issue:
Description:
Measure:time to recurrence (cohort II in case of secondary resection)
Time Frame:up to 4 years
Safety Issue:
Description:
Measure:toxicity and feasibility
Time Frame:up to about 6 month
Safety Issue:
Description:number of patients with adverse events and severity according to NCI CTC 3.0
Measure:liver toxicity for resected patients (central histological review); biopsies should be obtained for all patients pre-treatment
Time Frame:up to 1 year
Safety Issue:
Description:histological findings according to CASH/SOS scores
Measure:QL (QLQ C30)
Time Frame:Pre-treatment, before start of every 3rd cycle and at the end of treatment
Safety Issue:
Description:scores according to EORTC QLQ-C30 scoring manual (Quality of life)
Measure:translational research (EGFR genetics and proteomics): prognostic and predictive impact on efficacy outcomes
Time Frame:up to 4 years
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AIO-Studien-gGmbH

Last Updated

January 20, 2017