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

Study Overview
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Brief Summary
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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

Detailed Description
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Phase II, open-label, non-randomized study that will be conducted in two sequential cohorts of patients. Patients with metastatic colorectal cancer not amenable to any clinical improvement by current standard treatments are planned to be enrolled.

Official Title
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NGR005: Pilot Study of NGR-hTNF Administered at Low and High Doses in Combination With a Standard Oxaliplatin Based Regimen in Patients With Metastatic Colorectal Cancer

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: NGR-hTNF
* Drug: Oxaliplatin
* Drug: capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: NGR-hTNF<br>* iv 0.8 or 45 mcg/sqm q3W<br>Drug: Oxaliplatin<br>* iv q3W 100 mg/sqm 60 minutes after NGR-hTNF infusion<br>Drug: capecitabine<br>* orally 825 mg/sqm 2qDx14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGR-hTNF, Capecitabine, Oxaliplatin, Colon cancer