Investigation of efficacy and safety of panitumumab in combination with irinotecan/5-fluorouracil/leucovorin (FOLFIRI) in patients with colorectal cancer liver metastasis
- Conditions
- previously untreated, wild-type RAS, potentially resectable colorectal cancer liver metastasesTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-000265-20-AT
- Lead Sponsor
- ABCSG (Austrian Breast & Colorectal Cancer Study Group)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
- histologically confirmed metastatic colorectal cancer with potentially resectable liver metastases
- primary tumor in-situ or resected (in case of resected primary tumor, neoadjuvant short-time radiotherapy is allowed if terminated > 14 days prior to registration)
- subjects with wild-type RAS tumor status confirmed by assessment of paraffin embedded tumor tissue from the primary tumor or metastases
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- at least one measurable metastatic lesion in the liver as per RECIST 1.1 guidelines using multislice 3 phase CT
- man or woman > 18 years
- hematologic function, as follows (< 28 days of registration): absolute neutrophil count (ANC) > 1.5 x 109/L; leucocyte count > 3.0 x 109g/L; platelet count > 100 x 109/L; hemoglobin > 9 x g/dL
- renal function, as follows (< 28 days of registration): creatinin < 1.5 x upper limit of normal (ULN)
- hepatic function, as follows (< 28 days of registration): aspartate aminotransferase (AST) < 5 x ULN in presence of liver metastases; alanine aminotransferase (ALT) < 5 x ULN in presence of liver metastases; total bilirubin < 1.5 x ULN
- women of childbearing potential must have a negative pregnancy test done within 1 week before registration
- competent to comprehend, sign, and date an IEC/IRB-approved informed consent form
- life expectancy > 3 months
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18
- prior chemotherapy for the treatment of current metastatic cancer (including biologics)
- current extrahepatic metastatic disease
- prior chemotherapy and/or resection of any metastases from mCRC <5 years
- prior adjuvant or neoadjuvant (chemo-) therapy for the treatment of colorectal cancer = 26 weeks prior to registration
- radiotherapy = 14 days prior to registration (patients must have recovered from all radiotherapy-related toxicities)
- previous malignancy other than CRC in the last 5 years except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
- active infection requiring systemic treatment or any uncontrolled infections < 14 days prior to registration
- any investigational agent or therapy < 28 days before registration
- clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before registration
- known allergy or hypersensitivity to irinotecan, 5-FU, leucovorin or panitumumab
- history of severe adverse events to iodinated contrast agents
- history of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
- known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection
- any co-morbid disease or condition that could increase the risk of toxicity
- any uncontrolled concurrent illness or history of any medical condition that may interfere with the interpretation of the study results
- major surgical procedure (requiring general anaesthesia) < 28 days - patients must have recovered from surgery-related toxicities
- subject who is pregnant or breast feeding or planning to become pregnant within 6 months after the end of treatment
- woman or man of childbearing potential not consenting to use adequate contraceptive precautions (double barrier contraceptive methods e.g. diaphragm plus condom), or abstinence during the course of the study and 6 months after the last study drug administration
- subject unwilling or unable to comply with study requirements
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluation of efficacy and safety of perioperative treatment including panitumumab and FOLFIRI as first line therapy for mCRC in subjects with potentially resectable liver metastases expressing wild-type RAS;Secondary Objective: - evaluation of proportion of patients who respond after 4 cycles of therapy without liver tissue damage<br>- liver resection rate<br>- evaluation of perioperative morbidity and mortality<br>- evaluation of pathological response acc. to tumor regression rate<br>- progression-free survival time (PFS)<br>- overall survival (OS);Primary end point(s): objective response rate (ORR);Timepoint(s) of evaluation of this end point: after neoadjuvant therapy (4 cycles)
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - evaluation of ORR without liver tissue damage<br>- resection rate<br>- evaluation of perioperative morbidity and mortality<br>- proportion of subjects with a complete pathological response<br>- progression-free survival time (PFS)<br>- overall survival (OS);Timepoint(s) of evaluation of this end point: - ORR: after 4 cycles of therapy<br>- Resection rate: after neoadjuvant chemotherapy<br>- PFS: time from registration date to the date of first observed progression disease (PD) or death (whichever comes first)<br>- OS: time from registration date to the date of death.