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

March 30, 2011
April 8, 2014
April 2011
December 2016   (final data collection date for primary outcome measure)
overall response rate [ Time Frame: up to about 6 month ] [ Designated as safety issue: No ]
RECIST
Same as current
Complete list of historical versions of study NCT01328171 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
FOLFOXIRI With or Without Panitumumab in Metastatic Colorectal Cancer (VOLFI)
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

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Colorectal Cancer
  • 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
  • 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
  • Experimental: A (FOLFOXIRI + Panitumumab)
    FOLFOXIRI + Panitumumab
    Intervention: Drug: FOLFOXIRI + Panitumumab
  • Active Comparator: B (FOLFOXIRI)
    FOLFOXIRI
    Intervention: Drug: FOLFOXIRI
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
93
June 2017
December 2016   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Michael Geißler, MD, PhD 0049 711 3103 ext 2451 m.geissler@klinikum-esslingen.de
Germany
 
NCT01328171
AIO KRK 0109, 2009-017731-17
Yes
AIO-Studien-gGmbH
AIO-Studien-gGmbH
  • Amgen
  • ClinAssess GmbH
Principal Investigator: Michael Geißler, MD, PhD Department of Oncology and Gastroenterology, Academic Teaching Hospital Esslingen
AIO-Studien-gGmbH
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP