Solid TumorsPhase 1NCT00878111
Study of NGR-hTNF Administered at High Doses in Patient With Advanced or Metastatic Solid Tumour
A Phase 1 study testing NGR-hTNF in people with Solid Tumors, run by AGC Biologics S.p.A. at 1 site in Italy.
Trial summary
The main objective of the trial is to document the safety and antivascular effect of escalating doses of NGR-hTNF, from 60 mcg/sqm to 325 mcg/sqm, in patients affected by advanced or metastatic solid tumors not amenable of standard therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- NGR-hTNF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2009to Feb 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years with selected metastatic solid tumours recognized to be highly vascularised and not amenable to any clinical improvement by current standard treatments
- Colorectal cancer (CRC) patients previously resistant to standard systemic regimens (including biologic agents)
- Gastric cancer (GC) patients treated with no more than two standard systemic regimens for metastatic disease
- Hepatocellular carcinoma (HCC) patients previously resistant to standard systemic regimens
- Pancreatic carcinoma (PC) patients treated with no more than one standard systemic regimen for metastatic disease
- Non small cell lung carcinoma (NSCLC) patients treated with no more than two standard systemic regimens (including biologic agents) for metastatic disease
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- Neuroendocrine (NE) tumours refractory to somatostatin analogue treatment
- Other rare tumours including malignant pleural mesothelioma (MPM), soft-tissue sarcoma (STS), and renal cell carcinoma (RCC), resistant/refractory to current standard treatments
- 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 before treatment start:
- Chemotherapy, radiation therapy, hormonal therapy, or immunotherapy: wash-out period of 28 days
- Surgery: wash-out period of 14 days
- Patients must give written informed consent to participate in the study.
Who cannot join
- 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) > 450 ms
- Patient with significant peripheral vascular disease
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- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy), or history of stroke
- 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 or contraindications 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 child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: NGR013: Phase I and Pharmacodynamic Study of NGR-hTNF Administered at High Doses in Patients With Advanced or Metastatic Solid Tumour
The main objective of the trial is to document the safety and antivascular effect of escalating doses of NGR-hTNF, from 60 mcg/sqm to 325 mcg/sqm, in patients affected by advanced or metastatic solid tumors not amenable of standard therapies.
Safety will be established by clinical and laboratory assessment according to NCI-CTCAE criteria (version 4.02).
Read the detailed description
Pre-clinical studies provide the support that NGR-TNF is endowed with a higher therapeutic index in animal models and studies of the mechanism of action showed that NGR-TNF can induce tumour necrosis when used at relatively high doses.
Recently, a phase I dose-escalation study of NGR-hTNF has explored the dose range between 0.2 and 60 µg/m2, showing DLT at 60 mcg/m2 experienced as transient acute infusion reaction few minutes after the first administration start. Considering the relationship with the infusion of these events, a further dose escalation will be explored in the present phase I study by using both a longer infusion time (i.e., 120 minutes instead of 60 minutes) and a mild premedication.
The first cohort (n=4) of patients will be treated with NGR-hTNF administered at 60 mcg/m2 IV every three weeks, that is a dose level 33% higher than MTD and recommended dose selected in the previous phase I trial (i.e., 45 mcg/m2). If ≤1 of 4 patients experience DLT during the first cycle, following cohorts will be treated with escalating doses (from 80 to 325 mcg/m2) of NGR-hTNF IV every three weeks.
- Conditions
- Solid Tumors
- Being tested
- NGR-hTNF
- Keywords
- NGR-hTNF, Solid tumours, High doses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGR-hTNFDrug
First cohort: iv q3W 60 mcg/sqm over 120 min*
Second cohort: iv q3W 80 mcg/sqm over 120 min*
Third cohort: iv q3W 100 mcg/sqm over 120 min*
Fourth cohort: iv q3W 125 mcg/sqm over 120 min*
Fifth cohort: iv q3W 150 mcg/sqm over 120 min*
Sixth cohort: iv q3W 175 mcg/sqm over 120 min*
Seventh cohort: iv q3W 200 mcg/sqm over 120 min*
Eighth cohort: iv q3W 225 mcg/sqm over 120 min*
Ninth cohort: iv q3w 250 mcg/sqm over 120 min*
Tenth cohort: iv q3w 275 mcg/sqm over 120 min*
Eleventh cohort: iv q3w 300 mcg/sqm over 120 min*
Twelfth cohort: iv q3w 325 mcg/sqm over 120 min*
- If the first infusion is well-tolerated, the second infusion may be delivered over 90 minutes. If the 90-minute infusion is well tolerated, all subsequent infusions may be delivered over a 60-minute period.
| Study group | Role | What they receive |
|---|---|---|
| A: escalating dose levels of NGR-hTNF | Experimental | NGR-hTNF administered at high doses Receives: Drug: NGR-hTNF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Optimal Biologic Dose (OBD)
Evaluating both the safety in terms of maximum tolerated dose (MTD) and the antivascular effect in terms of changes documented with dynamic imaging (DCE-MRI)
Measured: Before treatment, every 3-6 weeks and at the end of treatment
Secondary outcomes (2)
Pharmacokinetic
Evaluation of plasma levels of sTNF-RI and sTNF-RII and anti-NGR-hTNF antibodies
Measured: Several time points after 1st, 2nd and 3rd administration
Preliminary antitumor activity
In terms of objective response rate according to RECIST criteria, progression-free and overall survival.
Measured: Every 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2009 (estimated)
- Study startApr 2009
- Primary completionFeb 2017
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- AGC Biologics S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antonio Lambiase, MD, Study director, AGC Biologics S.p.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878111
- Sponsor's protocol ID
- NGR013
- Other IDs
- 2008-000816-33, 2008
- Status last verified
- Aug 2018
- First submitted
- 7 Apr 2009
- Last updated
- 29 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NGR013: Phase I and Pharmacodynamic Study of NGR-hTNF Administered at High Doses in Patients With Advanced or Metastatic Solid Tumour
- ClinicalTrials.gov ID
- NCT00878111
- Acronym / sponsor ID
- NGR013
- Conditions
- Solid Tumors
- Keywords
- NGR-hTNF, Solid tumours, High doses
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- AGC Biologics S.p.A.Industry (pharma, biotech, devices)
- Study start
- Apr 2009
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 8 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of the trial is to document the safety and antivascular effect of escalating doses of NGR-hTNF, from 60 mcg/sqm to 325 mcg/sqm, in patients affected by advanced or metastatic solid tumors not amenable of standard therapies.
Safety will be established by clinical and laboratory assessment according to NCI-CTCAE criteria (version 4.02).
Detailed description
Pre-clinical studies provide the support that NGR-TNF is endowed with a higher therapeutic index in animal models and studies of the mechanism of action showed that NGR-TNF can induce tumour necrosis when used at relatively high doses.
Recently, a phase I dose-escalation study of NGR-hTNF has explored the dose range between 0.2 and 60 µg/m2, showing DLT at 60 mcg/m2 experienced as transient acute infusion reaction few minutes after the first administration start. Considering the relationship with the infusion of these events, a further dose escalation will be explored in the present phase I study by using both a longer infusion time (i.e., 120 minutes instead of 60 minutes) and a mild premedication.
The first cohort (n=4) of patients will be treated with NGR-hTNF administered at 60 mcg/m2 IV every three weeks, that is a dose level 33% higher than MTD and recommended dose selected in the previous phase I trial (i.e., 45 mcg/m2). If ≤1 of 4 patients experience DLT during the first cycle, following cohorts will be treated with escalating doses (from 80 to 325 mcg/m2) of NGR-hTNF IV every three weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A: escalating dose levels of NGR-hTNF | Experimental | Drug: NGR-hTNFNGR-hTNF administered at high doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients ≥18 years with selected metastatic solid tumours recognized to be highly vascularised and not amenable to any clinical improvement by current standard treatments
- Life expectancy more than 3 months
- ECOG Performance status 0-1
- Adequate baseline bone marrow, hepatic and renal function, defined as follows:
- Patients may have had prior therapy providing the following conditions are met before treatment start:
Key exclusion criteria (11 listed)
- 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) > 450 ms
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGR-hTNFFirst cohort: iv q3W 60 mcg/sqm over 120 min* Second cohort: iv q3W 80 mcg/sqm over 120 min* Third cohort: iv q3W 100 mcg/sqm over 120 min* Fourth cohort: iv q3W 125 mcg/sqm over 120 min* Fifth cohort: iv q3W 150 mcg/sqm over 120 min* Sixth cohort: iv q3W 175 mcg/sqm over 120 min* Seventh cohort: iv q3W 200 mcg/sqm over 120 min* Eighth cohort: iv q3W 225 mcg/sqm over 120 min* Ninth cohort: iv q3w 250 mcg/sqm over 120 min* Tenth cohort: iv q3w 275 mcg/sqm over 120 min* Eleventh cohort: iv q3w 300 mcg/sqm over 120 min* Twelfth cohort: iv q3w 325 mcg/sqm over 120 min* * If the first infusion is well-tolerated, the second infusion may be delivered over 90 minutes. If the 90-minute infusion is well tolerated, all subsequent infusions may be delivered over a 60-minute period. | Drug | A: escalating dose levels of NGR-hTNF |
Primary outcome
Optimal Biologic Dose (OBD)
Time frame: Before treatment, every 3-6 weeks and at the end of treatment
Evaluating both the safety in terms of maximum tolerated dose (MTD) and the antivascular effect in terms of changes documented with dynamic imaging (DCE-MRI)
2 secondary outcomes
Pharmacokinetic
Time frame: Several time points after 1st, 2nd and 3rd administration
Preliminary antitumor activity
Time frame: Every 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Lambiase, MD study director
AGC Biologics S.p.A.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NGR-hTNF in people with Solid Tumors, run by AGC Biologics S.p.A. at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Optimal Biologic Dose (OBD) (time frame: Before treatment, every 3-6 weeks and at the end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2018.