Study of NGR-hTNF as Single Agent in Patients Affected by Colorectal Cancer (CRC)

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: NGR-hTNF

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Genoa, Italy
    • Azienda Ospedaliera Universitaria "San Martino"
  • Milan, Italy
    • Fondazione San Raffaele del Monte Tabor
  • Milan
    • Rozzano, Milan, Italy
      • Istituto Clinico Humanitas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: NGR-hTNF; NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every 3 weeks or weekly	Drug: NGR-hTNF; iv q3W or q1W NGR-hTNF 0.8 μg/m²

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS evaluated according to Response evaluation criteria in solid tumors (RECIST)	during the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Growth Control Rate (TGCR)	TGCR evaluated according to Response evaluation criteria in solid tumors (RECIST)	during the study
Overall survival (OS)	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	during the study
Circulating tumor cells (CTCs)	To document modification of CTCs	before and following the treatment
Experimental imaging study (DCE-MRI)	to document possible modifications on vessels permeability	before and following the first cycle
to evaluate AUC(tau) of NGR-hTNF in patients treated with weekly schedule	to evaluate AUC(tau) of NGR-hTNF administered weekly	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 in patients treated with weekly schedule	to evaluate Cmax of NGR-hTNF administered weekly	during the first 6 weeks (time points: prior to infusion, 20 minutes, 60 minutes, 90 minutes, 120 minutes and 240 minutes after treatment start)
Safety according to NCI-CTCAE criteria (version 3)	To evaluate safety profile related to NGR-hTNF	during and following the treatment

Collaborators and Investigators

• Sponsor: AGC Biologics S.p.A.
• Investigators: Principal Investigator: Federico Caligaris Cappio, MD, Fondazione San Raffaele del Monte Tabor

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: June 5, 2007
• First Submitted That Met QC Criteria: June 5, 2007
• First Posted (Estimate): June 6, 2007

Study Record Updates

• Last Update Posted (Actual): January 16, 2019
• Last Update Submitted That Met QC Criteria: January 14, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: NGR-hTNF; CRC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: NGR006; 2006-005451-15 (EudraCT Number)