NGR-hTNF Administered in Combination With a Standard Oxaliplatin Based Regimen in Patients With Metastatic Colorectal Cancer

NCT00675012 | Completed Phase 2

• 2 other identifiers: NGR0052007-003668-24
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the trial is to document the safety of NGR-hTNF administered at low and high doses in combination with a standard oxaliplatin based regimen in patients with metastatic colorectal cancer not amenable to any clinical improvement by current standard treatments

Conditions

Colon Cancer

Keywords

NGR-hTNF; Capecitabine; Oxaliplatin; Colon cancer

Outcome Measures

Primary Outcomes (1)

• To determine the feasibility and safety of NGRhTNF administered at low (0.8 mcg/sqm) and high (45 mcg/sqm) doses in combination with a standard oxaliplatin-based regimen in two sequential cohorts of patients with metastatic colorectal cancer.

  during the study

Secondary Outcomes (2)

• Document the preliminary antitumor activity in terms of objective response rate (according to RECIST criteria) and progression-free survival

  during the study

• Evaluate the pharmacokinetic profile of NGRhTNF and to measure plasma levels of sTNF-RI and sTNF-RII

  before during and following the treatment

Study Arms (1)

A

EXPERIMENTAL

Drug: NGR-hTNF; Drug: Oxaliplatin; Drug: capecitabine

Interventions

NGR-hTNF DRUG

iv 0.8 or 45 mcg/sqm q3W

A

Oxaliplatin DRUG

iv q3W 100 mg/sqm 60 minutes after NGR-hTNF infusion

A

capecitabine DRUG

orally 825 mg/sqm 2qDx14

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years with metastatic colorectal cancer (CRC) treated with no more than three standard systemic regimens (including biologic agents) for metastatic disease
• Life expectancy more than 3 months
• ECOG Performance status 0-1
• 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 metastasis
• AST and/or ALT \<5 x ULN in presence of liver metastasis
• Serum creatinine \<1.5 x ULN
• Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50 ml/min
• Patients may have had prior therapy providing the following conditions are met:
• Chemotherapy, radiation therapy, hormonal therapy or immunotherapy: wash-out period of 28 days before start treatment
• Surgery: wash-out period of 14 days before start treatment
• Patients must give written informed consent to participate in the study

You may not qualify if:

• Concurrent anticancer therapy
• Patients must not receive any other investigational agents while on study
• Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
• Uncontrolled hypertension
• Prolonged QTc interval (congenital or acquired)
• Patient with significant peripheral vascular disease
• 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
• Symptomatic peripheral neuropathy ≥ grade 1 according the NCI CTCAE v.3.0.
• Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients
• Known hypersensitivity/allergic reaction or contraindications to platinum compounds or fluoropyrimidines
• 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

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (1)

Azienda Ospedaliera Universitaria San Martino

Genoa, Genoa, 16132, Italy

Location

Related Publications (1)

• Mammoliti S, Andretta V, Bennicelli E, Caprioni F, Comandini D, Fornarini G, Guglielmi A, Pessino A, Sciallero S, Sobrero AF, Mazzola G, Lambiase A, Bordignon C. Two doses of NGR-hTNF in combination with capecitabine plus oxaliplatin in colorectal cancer patients failing standard therapies. Ann Oncol. 2011 Apr;22(4):973-978. doi: 10.1093/annonc/mdq436. Epub 2010 Sep 20.

  PMID: 20855468 RESULT

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

tumor necrosis factor-alpha, CNGRC fusion protein, human; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Alberto Sobrero, MD

  Azienda Ospedaliera Universitaria San Martino Genoa, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: May 8, 2008
• Study Start: December 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: May 1, 2013
• Last Updated: May 30, 2014

Record last verified: 2014-05

Locations

IT (1)