Colorectal Cancer (CRC)
Conditions
Keywords
NGR-hTNF, CRC
Brief summary
The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic colorectal cancer patients treated with NGR-hTNF as single agent. Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria.
Detailed description
This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic colorectal cancer (CRC), previously treated with fluoropyrimidine, oxaliplatin and irinotecan based regimens, that will be conducted using Simon's two-stage design method.
Interventions
DRUGNGR-hTNF
iv q3W or q1W NGR-hTNF 0.8 μg/m²
Sponsors
AGC Biologics S.p.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients \>18 years affected by advanced or metastatic colorectal cancer (CRC), previously treated with fluoropyrimidine, oxaliplatin and irinotecan based regimens, but not more than three lines of therapy. Adjuvant chemotherapy following definitive management of the primary lesion in the colon or rectum is allowed and will not be counted as a line of therapy * ECOG Performance status 0 - 1 * Patients in progression disease at study entry, CT documented * Adequate baseline bone marrow, hepatic and renal function, defined as follows: * Neutrophils \> 1.5 x 10\^9/L and platelets \> 100 x 10\^9/L * Bilirubin \< 1.5 x ULN * AST and/or ALT \< 2.5 x ULN in absence of liver metastases * AST and/or ALT \< 5 x ULN in presence of liver metastases * Serum creatinine \< 1.5 x ULN * Absence of any conditions in which hypervolemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or hemodilution could represent a risk for the patient (reference appendix Technical data sheet human albumin) * Normal cardiac function and absence of uncontrolled hypertension * Patients must give written informed consent to participate in the study
Exclusion criteria
* More than three lines of chemotherapy (except biological agents) * Concurrent anticancer therapy * Patients may not receive any other investigational agents while on study * Clinical signs of CNS involvement * Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol * Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol * Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e.menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | during the study | PFS evaluated according to Response evaluation criteria in solid tumors (RECIST) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | during the study | Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive |
| Circulating tumor cells (CTCs) | before and following the treatment | To document modification of CTCs |
| Experimental imaging study (DCE-MRI) | before and following the first cycle | to document possible modifications on vessels permeability |
| Tumor Growth Control Rate (TGCR) | during the study | TGCR evaluated according to Response evaluation criteria in solid tumors (RECIST) |
| to evaluate Cmax of NGR-hTNF in patients treated with weekly schedule | during the first 6 weeks (time points: prior to infusion, 20 minutes, 60 minutes, 90 minutes, 120 minutes and 240 minutes after treatment start) | to evaluate Cmax of NGR-hTNF administered weekly |
| Safety according to NCI-CTCAE criteria (version 3) | during and following the treatment | To evaluate safety profile related to NGR-hTNF |
| to evaluate AUC(tau) of NGR-hTNF in patients treated with weekly schedule | during the first 6 weeks (time points: prior to infusion, 20 minutes, 60 minutes, 90 minutes, 120 minutes and 240 minutes after treatment start) | to evaluate AUC(tau) of NGR-hTNF administered weekly |
Countries
Italy
Outcome results
None listed