NGR-TNF in Treating Patients With Advanced Solid Tumors
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer Head and Neck Cancer Kidney Cancer Unspecified Adult Solid Tumor, Protocol Specific |
Biological: CNGRC peptide-TNF alpha conjugate |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Trial of NGR-TNF Administered Every 3 Weeks as a 1 Hour Intravenous Infusion in Patients With Solid Tumor |
- Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0 [ Designated as safety issue: Yes ]
- Clinical response as measured by RECIST criteria [ Designated as safety issue: No ]
- Mechanism of action as measured by Dynamic Imaging [ Designated as safety issue: No ]
| Enrollment: | 70 |
| Study Start Date: | September 2004 |
| Primary Completion Date: | November 2007 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Germany | |
| University Medical Center Hamburg - Eppendorf | |
| Hamburg, Germany, D-20246 | |
| Netherlands | |
| Universitair Medisch Centrum St. Radboud - Nijmegen | |
| Nijmegen, Netherlands, NL-6500 HB | |
| Study Chair: | Cornelis J. A. Punt, MD, PhD | Universitair Medisch Centrum St. Radboud - Nijmegen |
More Information
Additional Information:
Publications:
| Responsible Party: | European Organisation for Research and Treatment of Cancer - EORTC |
| ClinicalTrials.gov Identifier: | NCT00098943 History of Changes |
| Other Study ID Numbers: | EORTC-16041, EORTC-16041, MOLMED-EORTC-16041, EUDRACT-2004-000950-21 |
| Study First Received: | December 8, 2004 |
| Last Updated: | September 20, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
|
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 stage IV squamous cell carcinoma of the nasopharynx stage IV squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity recurrent verrucous carcinoma of the larynx recurrent verrucous carcinoma of the oral cavity stage IV verrucous carcinoma of the oral cavity stage IV verrucous carcinoma of the larynx recurrent adenoid cystic carcinoma of the oral cavity stage IV adenoid cystic carcinoma of the oral cavity recurrent basal cell carcinoma of the lip |
Additional relevant MeSH terms:
|
Carcinoma, Renal Cell Kidney Neoplasms Colorectal Neoplasms Head and Neck Neoplasms Neoplasms Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Urologic Neoplasms Urogenital Neoplasms |
Neoplasms by Site Kidney Diseases Urologic Diseases Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases |
ClinicalTrials.gov processed this record on June 18, 2013