NGR-TNF in Treating Patients With Advanced Solid Tumors

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

CNGRC peptide-TNF alpha conjugate

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring 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, stage IV basal cell carcinoma of the lip, recurrent mucoepidermoid carcinoma of the oral cavity, stage IV mucoepidermoid carcinoma of the oral cavity, recurrent lymphoepithelioma of the nasopharynx, recurrent lymphoepithelioma of the oropharynx, stage IV lymphoepithelioma of the nasopharynx, stage IV lymphoepithelioma of the oropharynx, recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity, stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity, recurrent inverted papilloma of the paranasal sinus and nasal cavity, recurrent midline lethal granuloma of the paranasal sinus and nasal cavity, stage IV inverted papilloma of the paranasal sinus and nasal cavity, stage IV midline lethal granuloma of the paranasal sinus and nasal cavity, metastatic parathyroid cancer, recurrent parathyroid cancer, recurrent salivary gland cancer, stage IV salivary gland cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Medical Center Hamburg - Eppendorf
Universitair Medisch Centrum St. Radboud - Nijmegen

Outcomes

Primary Outcome Measures

Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0

Secondary Outcome Measures

Clinical response as measured by RECIST criteria

Mechanism of action as measured by Dynamic Imaging

Full Information

NCT ID

NCT00098943

First Posted

December 8, 2004

Last Updated

September 20, 2012

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

1. Study Identification

Unique Protocol Identification Number

NCT00098943

Brief Title

NGR-TNF in Treating Patients With Advanced Solid Tumors

Official Title

Phase I Trial of NGR-TNF Administered Every 3 Weeks as a 1 Hour Intravenous Infusion in Patients With Solid Tumor

Study Type

Interventional

2. Study Status

Record Verification Date

September 2012

Overall Recruitment Status

Completed

Study Start Date

September 2004 (undefined)

Primary Completion Date

November 2007 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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, 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, stage IV basal cell carcinoma of the lip, recurrent mucoepidermoid carcinoma of the oral cavity, stage IV mucoepidermoid carcinoma of the oral cavity, recurrent lymphoepithelioma of the nasopharynx, recurrent lymphoepithelioma of the oropharynx, stage IV lymphoepithelioma of the nasopharynx, stage IV lymphoepithelioma of the oropharynx, recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity, stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity, recurrent inverted papilloma of the paranasal sinus and nasal cavity, recurrent midline lethal granuloma of the paranasal sinus and nasal cavity, stage IV inverted papilloma of the paranasal sinus and nasal cavity, stage IV midline lethal granuloma of the paranasal sinus and nasal cavity, metastatic parathyroid cancer, recurrent parathyroid cancer, recurrent salivary gland cancer, stage IV salivary gland cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Masking

None (Open Label)

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

CNGRC peptide-TNF alpha conjugate

Primary Outcome Measure Information:

Title

Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 3.0

Secondary Outcome Measure Information:

Title

Clinical response as measured by RECIST criteria

Title

Mechanism of action as measured by Dynamic Imaging

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cornelis J. A. Punt, MD, PhD

Organizational Affiliation

Universitair Medisch Centrum St. Radboud - Nijmegen

Official's Role

Study Chair

Facility Information:

Facility Name

University Medical Center Hamburg - Eppendorf

City

Hamburg

ZIP/Postal Code

D-20246

Country

Germany

Facility Name

Universitair Medisch Centrum St. Radboud - Nijmegen

City

Nijmegen

ZIP/Postal Code

NL-6500 HB

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

20145168

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Colorectal Cancer, Head and Neck Cancer, Kidney Cancer

About this trial

Eligibility Criteria

Sites / Locations

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial