Trial of TRX518 (Anti-GITR mAb) in Stage III or IV Malignant Melanoma or Other Solid Tumors - Full Text View

Purpose

TRX518-001 is an open label, non-randomized single group assignment, Phase 1 single dose escalation study in adults with biopsy proven unresectable Stage III or Stage IV melanoma or other solid tumor malignancies. The study objectives are to determine the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of TRX518 and to define the maximum tolerated dose at which there are tolerable side effects and/or maximum PK/PD parameter changes.

Subjects will be assigned to a cohort in the order screening is completed. Dose will depend upon the cohort in which a subject is enrolled and cohorts will be dosed consecutively by ascending dose.

MSKCC Study #10-147

Condition	Intervention	Phase
Unresectable Stage III or Stage IV Malignant Melanoma or Other Solid Tumor Malignancies	Biological: TRX518	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A First-in-Human Single Ascending Dose Study of TRX518 in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma or Other Solid Tumor Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Genetic and Rare Diseases Information Center resources: Carcinoid Tumor Neuroepithelioma

U.S. FDA Resources

Further study details as provided by GITR, Inc.:

Primary Outcome Measures:

1. Adverse events (Safety) [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
Any adverse change in health or side effect from the initiation of the study drug dose through completion or premature withdrawal.
2. Pharmacokinetics (PK) [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Observations of the distribution, duration of effects and chemical changes of TRX518 in the body and the effects and routes of the body's elimination of TRX518.
3. Pharmacodynamics (PD) [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Observation of the effects of TRX518 on the body and immune system.

Secondary Outcome Measures:

Observation of effects, if any, on circulating lymphoid cell number and function, TRX518 potential immunogenicity, and TRX518 long term safety as reflected by adverse event reports at 6 - 24 months after a single dose. [ Time Frame: 6, 12, 18, 24 months ] [ Designated as safety issue: No ]


Estimated Enrollment:	40
Study Start Date:	October 2010
Estimated Study Completion Date:	March 2016
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TRX518	Biological: TRX518 Humanized, Fc disabled, anti-human GITR (glucocorticoid-induced tumor necrosis factor receptor) monoclonal antibody

Detailed Description:

The following visits are required:

Screening visit: 1 to 2 appointments will be conducted to determine eligibility. All or most requirements can be determined from the patient's medical records.
Baseline visit: within 7 days of the planned study dosing day a baseline physical exam, blood tests and electrocardiogram will be obtained.
Dosing visit: 1 outpatient visit where TRX518 will be given IV over 1 hour followed by 4 hours of observation and some repeat blood tests.
Follow up visits: 5 outpatient visits following dosing at 1, 8 and 15 days and 3, 6, 12, and 18 weeks post dosing
Long term follow-up: 4 brief assessments by medical record review and/or telephone contact at 6, 12, 18, and 24 months post dosing.
The core study duration is 18 weeks. The follow-up study duration is 24 months.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

18 years or older at the time of dose initiation.
Unresectable Stage III or Stage IV biopsy proven malignant melanoma or other solid tumor malignancies, with at least 1 measurable lesion, who have failed to respond to or relapsed following standard treatment or who have declined to pursue standard treatment, in otherwise stable health (as confirmed by medical history, physical examination, ECG, and screening laboratory tests).
Expected survival of at least 12 weeks after dosing.
Karnofsky Performance Status ≥70 in the 7 day baseline period immediately prior to dosing.
Evidence of adequate organ function by standard laboratory tests.
All female subjects of child bearing age must be either surgically sterile, postmenopausal for at least 1 year, or using an acceptable method of contraception. Adequate contraception for both male and female subjects must be used from the beginning of the screening period until at least 8 weeks after the last dose of TRX518.

Exclusion Criteria:

Evidence of progression of central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosing.
Ocular melanoma.
Any major surgery within 6 weeks prior to dosing.
Any history of antitumor therapy (standard or experimental) completed within 30 days prior to dosing.
Any concomitant serious physical illness other than cancer (i.e., immune deficiency disease, bleeding disorder, etc.) within 1 year prior to dosing. Specifically, no history of autoimmune disease.
Clinically significant heart disease, defined as NYHA Class III or IV.

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: NCT01239134

Locations


United States, New York
Melanoma and Sarcoma Service / Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Ruth-Ann Roman 646-888-2395 romanr@mskcc.org
Principal Investigator: Jedd Wolchok, MD, PhD
United States, Ohio
Siedman Cancer Center / University Hospitals of Cleveland	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Henry Koon, MD 216-844-3951 henry.koon@uhhospitals.org
Principal Investigator: Henry Koon, MD
Taussig Cancer Institute / Cleveland Clinic Foundation	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Vamsidhar Velcheti, MD 216-444-8665 velchev@ccf.org
Principal Investigator: Vamsidhar Velcheti, MD

Sponsors and Collaborators

GITR, Inc.

Cancer Research Institute, New York City

Investigators


Principal Investigator:	Principle Investigator: Jedd Wolchok, MD, PhD	Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Melanoma Trials at MSKCC This link exits the ClinicalTrials.gov site


Responsible Party:	GITR, Inc.
ClinicalTrials.gov Identifier:	NCT01239134 History of Changes
Other Study ID Numbers:	TRX518-001
Study First Received:	November 9, 2010
Last Updated:	November 18, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by GITR, Inc.:


Malignant melanoma Metastatic Unresectable Stage III or Stage IV Solid tumor

Additional relevant MeSH terms:


Melanoma Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors	Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Nerve Tissue Nevi and Melanomas

ClinicalTrials.gov processed this record on September 23, 2016

Trial of TRX518 (Anti-GITR mAb) in Stage III or IV Malignant Melanoma or Other Solid Tumors (TRX518-001)