Clinical trial NCT00483080: Study of NGR-hTNF as Single Agent in Patients Affected by Colorectal Cancer (CRC)
Official title: NGR006: A Phase II Study of NGR-hTNF Administered as Single Agent Every 3 Weeks or Weekly in Patients Affected by Colorectal Cancer (CRC), Previously Treated With Fluoropyrimidine, Oxaliplatin and Irinotecan Based Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer (CRC)
Keywords: NGR-hTNF
CRC
Lead sponsor: AGC Biologics S.p.A.
Sponsor class: INDUSTRY
First posted: 2007-06-06
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: during the study
Secondary outcomes:
measure: Tumor Growth Control Rate (TGCR)
timeFrame: during the study
measure: Overall survival (OS)
timeFrame: during the study
measure: Circulating tumor cells (CTCs)
timeFrame: before and following the treatment
measure: Experimental imaging study (DCE-MRI)
timeFrame: before and following the first cycle
measure: to evaluate AUC(tau) of NGR-hTNF in patients treated with weekly schedule
timeFrame: during the first 6 weeks (time points: prior to infusion, 20 minutes, 60 minutes, 90 minutes, 120 minutes and 240 minutes after treatment start)
measure: to evaluate Cmax of NGR-hTNF in patients treated with weekly schedule
timeFrame: during the first 6 weeks (time points: prior to infusion, 20 minutes, 60 minutes, 90 minutes, 120 minutes and 240 minutes after treatment start)
measure: Safety according to NCI-CTCAE criteria (version 3)
timeFrame: during and following the treatment
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Genoa
country: Italy
facility: Azienda Ospedaliera Universitaria "San Martino"
city: Milan
country: Italy
facility: Fondazione San Raffaele del Monte Tabor
Study officials:
affiliation: Fondazione San Raffaele del Monte Tabor
name: Federico Caligaris Cappio, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Santoro A, Rimassa L, Sobrero AF, Citterio G, Sclafani F, Carnaghi C, Pessino A, Caprioni F, Andretta V, Tronconi MC, Finocchiaro G, Rossoni G, Zanoni A, Miggiano C, Rizzardi GP, Traversari C, Caligaris-Cappio F, Lambiase A, Bordignon C. Phase II study of NGR-hTNF, a selective vascular targeting agent, in patients with metastatic colorectal cancer after failure of standard therapy. Eur J Cancer. 2010 Oct;46(15):2746-52. doi: 10.1016/j.ejca.2010.07.012. Epub 2010 Aug 12.