NGR-TNF in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00098943
First received: December 8, 2004
Last updated: September 20, 2012
Last verified: September 2012
  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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098943

Locations
Germany
University Medical Center Hamburg - Eppendorf
Hamburg, Germany, D-20246
Netherlands
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Cornelis J. A. Punt, MD, PhD Universitair Medisch Centrum St. Radboud - Nijmegen
  More Information

Additional Information:
Publications:
Van 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.

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
Colorectal Neoplasms
Head and Neck Neoplasms
Kidney Neoplasms
Neoplasms
Adenocarcinoma
Carcinoma
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Kidney Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on October 29, 2014