An Open-label, Phase II Clinical Trial of Panitumumab in Combination With FOLFIRI Chemotherapy as Second Line Treatment in Subjects With Metastatic Colorectal Cancer Expressing Wild-type KRAS and Who Had Progressed ≥ 6 Months After the Last Dose of the First Line Chemotherapy
- Men or women 18 years of age or older
- Competent to comprehend, sign, and date an Independent Ethics Committee
(IEC)/Institutional Review Board (IRB)-approved informed consent form
- Adenocarcinoma of the colon or rectum confirmed histologically or cytologically by
the investigator in subjects presenting metastatic disease
- Subjects with wild-type KRAS tumor status confirmed by central laboratory assessment
of paraffin-embedded tumor tissue from the primary tumor or metastasis.
- Radiologically documented progression of the disease according to modified RECIST
criteria, 6 months or more after the last dose of chemotherapy for mCRC.
- Only one previous chemotherapy regimen for mCRC, consisting of first line
chemotherapy based on fluoropyrimidines and oxaliplatin (prior adjuvant chemotherapy
based on fluoropyrimidine is permitted).
- At least 1 uni-dimensionally measurable lesion of at least 20 mm per modified RECIST
criteria. (All sites of disease must be evaluated ≤ 28 days prior to enrollment)
- If subject has prior history of cancer other than colorectal carcinoma, basal cell
carcinoma, or cervical carcinoma in situ, then subject must not have had treatment or
active disease within 5 years.
- Karnofsky performance status ≥ 70% at the time of enrolment in the study.
- Life expectancy ≥ 3 months
- Prior radiotherapy is acceptable (target lesions should not have been irradiated). At
least 14 days must have passed since the administration of the radiotherapy and all
signs of early toxicity must have remitted.
- Haematological function (within the 7 days prior to starting the study treatment)::
- Absolute Neutrophil Count(ANC) ≥ 1.5 x 109 cells/L
- Hemoglobin ≥ 9.0 g/dL
- Platelet count ≥ 100 x 109/L
- Kidney function (within the 7 days prior to starting the study treatment):
- Creatinine ≤ 1.5 mg/dL
- Liver function (within the 7 days prior to starting the study treatment):
- Aspartate Aminotransferase(AST) ≤ 3 x Upper Limit of Normal(ULN) (if liver
metastases, ≤ 5 x ULN)
- Alanine aminotransferase(ALT) ≤ 3 x ULN (if liver metastases, ≤ 5 x ULN)
- Bilirubin ≤ 2 x ULN
- Metabolic function (within the 7 days prior to starting the study treatment):
- Magnesium ≥ lower limit of normal Lower Limit of normal(LLN),
- Calcium ≥ lower limit of normal (LLN)
- More than one previous chemotherapy regimen for mCRC consisting of first line
chemotherapy based on fluoropyrimidines and/or oxaliplatin (patients receiving
first-line chemotherapy based on irinotecan are not candidate for this study).
- Progression of the disease during the first line treatment or less than 6 months
after completing the last cycle of first line chemotherapy for mCRC.
- Systemic chemotherapy, hormone treatment, immune therapy or experimental or approved
antibodies/proteins (e.g. bevacizumab) ≤ 30 days prior to inclusion.
- Unresolved toxicity from a prior systemic treatment which, in the investigator's
opinion, makes the subject unsuitable for inclusion.
- Metastasis in brain/central nervous system (exception: subjects who have been
treated, have asymptomatic metastases in the central nervous system and have not been
receiving steroids for at least the 30 days prior to inclusion in the study are
- Significant cardiovascular disease, including unstable angina pectoris or myocardial
infarction within the 6 months prior to the start of the study treatment, or history
of ventricular arrhythmia.
- Previous treatment with anti-EGFr antibodies (e.g. cetuximab) or treatment with small
molecule Epidermal Growth Factor Receptor (EGFr) tyrosine kinase inhibitors (e.g.
- History of interstitial pneumonia or pulmonary fibrosis or signs of interstitial
pneumonia or pulmonary fibrosis on the baseline chest X-ray.
- Treatment for systemic infection within the 14 days prior to starting the study
- Radiotherapy ≤ 14 days prior to inclusion. Patients must have recovered from all
- Active inflammatory bowel or other intestinal disease causing chronic diarrhoea
(defined as > 4 loose bowel movements per day).
- History of Gilbert's syndrome or dihydropyrimidine deficiency.
- History of any disease which could increase the risks associated to participation in
the study or interfere in the interpretation of the study results.
- Known positive test for infection by human immune deficiency virus, hepatitis C,
chronic active hepatitis B.
- Subject allergic to the ingredients of the study medication of protein A of
- Any comorbid disease which could increase the risk of toxicity.
- The subject presents a disorder of any kind which compromises his/her ability to
provide informed consent in writing and/or follow the study procedures.
- Any investigational agent within the 30 days prior to inclusion.
- Major surgery within the 28 days prior to study enrollment.
- Pregnant or breastfeeding women.
- Women or men of childbearing age who do not agree to use appropriate double barrier
contraceptive methods (e.g. diaphragm plus condom) or remain abstinent throughout the
study and for 6 months after the last administration of the study drug for women and
1 month for men.
- Subjects who do not wish to meet the study requirements or are unable to do so.