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 K-ras Wild Type
- 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
- K-ras wild-type (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
- 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.
- 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
- 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
- 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.