Colorectal CancerPhase 1NCT00098943
NGR-TNF in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing CNGRC peptide-TNF alpha conjugate in people with Colorectal Cancer and Head and Neck Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 2 sites in 2 countries.
Trial summary
RATIONALE: Targeted therapy with tumor necrosis factor combined with a fusion protein may stop the growth of solid tumors by stopping blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and best dose of NGR-TNF in treating patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Head and Neck Cancer, Kidney Cancer
- What is being tested?
- CNGRC peptide-TNF alpha conjugate
- How many people
- 70 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2004to Nov 2007
- 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
DISEASE CHARACTERISTICS:
- Diagnosis of advanced solid tumor not amenable to any clinical improvement by current standard treatments
- Preferably tumors well known to be very angiogenic (e.g., renal, colon, thyroid, and head and neck cancers)
- No clinical signs of CNS involvement
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- ECOG 0-2 OR
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
Hepatic
- Bilirubin < 1.5 times upper limit of normal (ULN)
- AST and/or ALT < 2.5 times ULN (5 times ULN in the presence of liver metastases)
Renal
- Creatinine < 1.5 times ULN
Cardiovascular
- Cardiac function normal
- No uncontrolled hypertension
- No condition in which hypovolemia and its consequences (e.g., increased stroke volume, elevated blood pressure) or hemodilution could represent a risk to the patient
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study participation
- No active or uncontrolled systemic infection
- No other uncontrolled disease, serious illness, or medical condition that would preclude study participation
- No known hypersensitivity/allergic reaction to human albumin preparations or any of the excipients
- No psychological, familial, sociological, or geographical condition that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 28 days since prior immunotherapy
Chemotherapy
- At least 28 days since prior chemotherapy and recovered
Endocrine therapy
- At least 28 days since prior hormonal therapy
Radiotherapy
- At least 28 days since prior radiotherapy and recovered
- No prior radiotherapy to > 25% of bone marrow reserve
Surgery
- More than 2 weeks since prior surgery
Other
- No other concurrent anticancer therapy
- No other concurrent investigational agents
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, NL-6500 HB
About this study
Official title: Phase I Trial of NGR-TNF Administered Every 3 Weeks as a 1 Hour Intravenous Infusion in Patients With Solid Tumor
RATIONALE: Targeted therapy with tumor necrosis factor combined with a fusion protein may stop the growth of solid tumors by stopping blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of NGR-TNF in treating patients with advanced solid tumors.
Read the detailed description
OBJECTIVES:
Primary
- Determine the dose-limiting toxicity and maximum tolerated dose of tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) in patients with advanced solid tumors.
- Determine the recommended phase II dose of this drug in these patients.
Secondary
- Determine the mechanism of action of this drug in these patients.
- Determine response in patients treated with this drug.
OUTLINE: This is an open-label, nonrandomized, dose-escalation, multicenter study.
Patients receive tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) IV over 1 hour on day 1. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
Cohorts of 1-6 patients receive escalating doses of NGR-TNF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients receive treatment at the MTD.
Patients are followed every 8 weeks until disease progression or the start of a new anticancer treatment.
PROJECTED ACCRUAL: A total of 1-30 patients will be accrued for this study.
- Conditions
- Colorectal Cancer, Head and Neck Cancer, Kidney Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- Being tested
- CNGRC peptide-TNF alpha conjugate
- Keywords
- unspecified adult solid tumor, protocol specific, stage IV renal cell cancer, recurrent renal cell cancer, stage IV colon cancer, recurrent colon cancer, anaplastic thyroid cancer, insular thyroid cancer, thyroid gland medullary carcinoma, stage IV follicular thyroid cancer, stage IV papillary thyroid cancer, recurrent thyroid cancer, recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the nasopharynx, recurrent squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the lip and oral cavity
- Medical subject headings
- Colorectal Neoplasms, Head and Neck Neoplasms, Kidney Neoplasms, Carcinoma, Renal Cell, Colonic Neoplasms, Thyroid Carcinoma, Anaplastic, Carcinoma, Medullary, Adenocarcinoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CNGRC peptide-TNF alpha conjugateBiological
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0
Secondary outcomes (2)
Clinical response as measured by RECIST criteria
Mechanism of action as measured by Dynamic Imaging
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2004 (estimated)
- Study startSep 2004
- Primary completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Cornelis J. A. Punt, MD, PhD, Study chair, Universitair Medisch Centrum St. Radboud - Nijmegen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098943
- Sponsor's protocol ID
- EORTC-16041
- Other IDs
- EORTC-16041, MOLMED-EORTC-16041, EUDRACT-2004-000950-21
- Status last verified
- Sep 2012
- First submitted
- 8 Dec 2004
- Last updated
- 24 Sep 2012
- Results posted
- No
Publications
van Laarhoven HW, Fiedler W, Desar IM, van Asten JJ, Marreaud S, Lacombe D, Govaerts AS, Bogaerts J, Lasch P, Timmer-Bonte JN, Lambiase A, Bordignon C, Punt CJ, Heerschap A, van Herpen CM. Phase I clinical and magnetic resonance imaging study of the vascular agent NGR-hTNF in patients with advanced cancers (European Organization for Research and Treatment of Cancer Study 16041). Clin Cancer Res. 2010 Feb 15;16(4):1315-23. doi: 10.1158/1078-0432.CCR-09-1621. Epub 2010 Feb 9.
PubMed 20145168Van Laarhoven H, Fiedler W, Desar IM, et al.: Phase I and DCE-MRI evaluation of NGR-TNF, a novel vascular targeting agent, in patients with solid tumors (EORTC 16041). [Abstract] J Clin Oncol 26 (Suppl 15): A-3521, 2008.
Heerschap A, Fiedler W, Marreaud S, et al.: A phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] J Clin Oncol 25 (Suppl 18): A-14074, 2007.
van Herpen C, Fiedler W, Marreaud S, et al.: A biological and pharmacologic phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-B78, 2007.
van Herpen C, Fiedler W, Toma S, et al.: Phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumours (EORTC 16041). [Abstract] European Journal of Cancer Supplements 4 (12): A-366, 113, 2006.
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of NGR-TNF Administered Every 3 Weeks as a 1 Hour Intravenous Infusion in Patients With Solid Tumor
- ClinicalTrials.gov ID
- NCT00098943
- Acronym / sponsor ID
- EORTC-16041
- Conditions
- Colorectal Cancer, Head and Neck Cancer, Kidney Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- Keywords
- unspecified adult solid tumor, protocol specific, stage IV renal cell cancer, recurrent renal cell cancer, stage IV colon cancer, recurrent colon cancer, anaplastic thyroid cancer, insular thyroid cancer, thyroid gland medullary carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Sep 2004
- Primary completion
- Nov 2007 (actual)
- First posted
- 9 Dec 2004 (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.
RATIONALE: Targeted therapy with tumor necrosis factor combined with a fusion protein may stop the growth of solid tumors by stopping blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of NGR-TNF in treating patients with advanced solid tumors.
Detailed description
OBJECTIVES:
Primary
- Determine the dose-limiting toxicity and maximum tolerated dose of tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) in patients with advanced solid tumors.
- Determine the recommended phase II dose of this drug in these patients.
Secondary
- Determine the mechanism of action of this drug in these patients.
- Determine response in patients treated with this drug.
OUTLINE: This is an open-label, nonrandomized, dose-escalation, multicenter study.
Patients receive tumor vasculature-targeted tumor necrosis factor alpha (NGR-TNF) IV over 1 hour on day 1. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
Cohorts of 1-6 patients receive escalating doses of NGR-TNF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients receive treatment at the MTD.
Patients are followed every 8 weeks until disease progression or the start of a new anticancer treatment.
PROJECTED ACCRUAL: A total of 1-30 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| CNGRC peptide-TNF alpha conjugate | Biological | – |
Primary outcome
Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0
2 secondary outcomes
Clinical response as measured by RECIST criteria
Mechanism of action as measured by Dynamic Imaging
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 24 Sep 2012.
- Results publication: PubMed 20145168van Laarhoven HW, Fiedler W, Desar IM, van Asten JJ, Marreaud S, Lacombe D, Govaerts AS, Bogaerts J, Lasch P, Timmer-Bonte JN, Lambiase A, Bordignon C, Punt CJ, Heerschap A, van Herpen CM. Phase I clinical and magnetic resonance imaging study of the vascular agent NGR-hTNF in patients with advanced cancers (European Organization for Research and Treatment of Cancer Study 16041). Clin Cancer Res. 2010 Feb 15;16(4):1315-23. doi: 10.1158/1078-0432.CCR-09-1621. Epub 2010 Feb 9.
- Results publicationVan Laarhoven H, Fiedler W, Desar IM, et al.: Phase I and DCE-MRI evaluation of NGR-TNF, a novel vascular targeting agent, in patients with solid tumors (EORTC 16041). [Abstract] J Clin Oncol 26 (Suppl 15): A-3521, 2008.
- Results publicationHeerschap A, Fiedler W, Marreaud S, et al.: A phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] J Clin Oncol 25 (Suppl 18): A-14074, 2007.
- Results publicationvan Herpen C, Fiedler W, Marreaud S, et al.: A biological and pharmacologic phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumors (EORTC 16041). [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-B78, 2007.
- Results publicationvan Herpen C, Fiedler W, Toma S, et al.: Phase I study of NGR-TNF, a novel vascular targeting agent, in patients with refractory solid tumours (EORTC 16041). [Abstract] European Journal of Cancer Supplements 4 (12): A-366, 113, 2006.
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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.
Cornelis J. A. Punt, MD, PhD study chair
Universitair Medisch Centrum St. Radboud - Nijmegen
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CNGRC peptide-TNF alpha conjugate in people with Colorectal Cancer and Head and Neck Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 24 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Netherlands. 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?
Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00098943, which also lists 5 linked publications.
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 24 Sep 2012.