Metastatic colorectal cancer refractory to irinotecan treatment
Conditions
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum. Metastatic colorectal adenocarcinoma not suitable for curative-intent treatment. Presence of at least one bidimensionally measurable lesion, not in a previously irradiated area. Immunohistochemical evidence of EGFR expression prior to study entry in primary tumor and/or at least one metastasis. Irinotecan 180 mg/m2 (210mg/m² is accepted), either as monotherapy or in combination with other agents, every 2 weeks for at least six weeks as most recent chemotherapy treatment. Up to two prior licensed dosage attenuations below 180mg/m² for irinotecan-associated toxicity are permitted. Time between last treatment and progression on the irinotecan-based therapy should not be longer than 90 days. Documented progression according to modified WHO criteria by comparison of CT or MRI scans on/after the irinotecan based therapy (new lung lesions may be documented by chest x-ray) whereby the time between documentation of progression and start of study treatment should not be longer than 90 days. At least one tumor site suitable for biopsy sampling. Still being able to tolerate therapy with irinotecan. Karnofsky performance status of ³ 80 at study entry. Effective contraception for both male and female patients if risk of conception exists. Neutrophils = 1.5 x 109/L, platelets = 100 x 109/L, and hemoglobin = 9 g/dL. Bilirubin level either normal or =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Brain metastasis (known or suspected). Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry. Having participated in another study within the preceding 30 days. Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol. Any investigational agent within 4 weeks prior to entry. Having received mitomycin C within 6 weeks prior to study entry. Any active dermatological condition > Grade 1. Previous exposure to EGFR pathway targeting therapy. Having previously participated in a study which included a possibility of being allocated to cetuximab therapy (whether or not the patient actually received cetuximab). Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months or left ventricular ejection fraction (LVEF) below the institutional range of normal. Acute or subacute intestinal occlusion or history of inflammatory bowel disease. Known allergic/hypersensitivity reaction to any of the components of the treatment. Pregnancy (absence confirmed by serum/urine b-HCG) or breast-feeding. Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix. Known drug abuse/ alcohol abuse. Legal incapacity or limited legal capacity medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare in skin biopsies the effects of an cetuximab dose escalation regimen on EGFR and downstream signaling pathway markers with those of the standard cetuximab regimen;Secondary Objective: To compare the percentages of patients experiencing Grade 2 or higher skin toxicity in patients randomized to receive cetuximab at the standard dosing regimen (dose group A) and in patients randomized to receive an escalating dosing regimen (dose group B) using NCI-CTC criteria, version 2.0. To compare the two treatment regimens (groups A and B) with respect to efficacy.·To compare the two treatment regimens (groups A and B) with respect to toxicity (safety and tolerability).·To investigate effects of higher cetuximab doses on EGFR and downstream signaling pathway markers in tumor.·To investigate the relationship between efficacy, skin toxicity and alterations in molecular profiles to identify pharmacogenomic markers that correlate with response or resistance.·To investigate differences in molecular markers between baseline and on-treatment samples·To perform evaluations of pharmacokinetics;Primary end point(s): Expression of EGFR and markers for the downstream signalling pathways in normal skin expressed by means of percentage of stained cells and staining intensity. IHC staining will allow a semi quantitative analysis of protein markers of the EGFR related signalling pathway. | — |
Countries
Italy, Sweden
Outcome results
None listed