Metastatic Colorectal Cancer
Conditions
Keywords
cetuximab rechallenge
Brief summary
This is a multicentric, phase II single-arm study in which KRAS, NRAS and BRAF wild-type, irinotecan-resistant metastatic colorectal cancer patients progressing after an initial response to a first-line cetuximab-containing therapy, receive a rechallenge third-line treatment with cetuximab plus irinotecan.
Interventions
DRUGcetuximab
DRUGirinotecan
Sponsors
Gruppo Oncologico del Nord-Ovest
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven diagnosis of colorectal adenocarcinoma; * RAS and BRAF wild-type status; * First-line irinotecan-based (FOLFIRI or FOLFOXIRI) cetuximab-containing therapy producing at least a partial response; * First-line progression-free survival in response to cetuximab-containing therapy ≥6 months; * Documentation of progression to first-line cetuximab within 4 weeks after last cetuximab administration; * Time between the end of first-line therapy and the start of third-line treatment with cetuximab plus irinotecan ≥4 months; * Second-line oxaliplatin-based (FOLFOXIRI, FOLFOX or XELOX) bevacizumab-containing therapy; * Documentation of progression to second-line treatment; * Measurable disease according to RECIST criteria v1.1; * Have tumor tissue (of primary tumor and metastases or at least one of the two) available for biomarker analysis; * Male or female patients \> 18 years of age; * ECOG Performance Status ≤ 2; * Life expectancy of at least 3 months; * Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment; * Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile or are sexually inactive; * Subjects and their partners must be willing to avoid pregnancy during the trial and until 6 months after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator, such as a two-barrier method or one-barrier method with spermicidal or intrauterine device. This requirement begins 2 weeks before receiving the first trial treatment and ends 6 months after receiving the last treatment; * Signed informed consent obtained before any study specific procedure.
Exclusion criteria
* Active uncontrolled infections or active disseminated intravascular coagulation; * Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix; * Fertile women (\< 12 months after last menstruation) and men of childbearing potential not willing to use effective means of contraception * Women who are pregnant or are breastfeeding; * Previous grade 3/4 infusion related reaction to cetuximab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| percentage of patients achieving a decrease equal or more than 30% in the sum of the longest diameters of target lesions | evaluation every 8 weeks until 48 weeks | ORR is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria. The determination of clinical response will be based on investigator-reported measurements. Responses will be evaluated with a chest and abdominal computed tomography (CT) scan every 8 weeks. Patients who do not have an on-study assessment will be included in the analysis as non-responders. |
Countries
Italy
Outcome results
None listed