Protocol Number: 07-C-0043

Title:

An Evaluation of the Tissue Distribution and the Selective Tumor Trafficking of TNF-Bound Colloidal Gold (CYT-6091) Following Intravenous Administration in Subjects with Primary and Metastatic Cancer Undergoing Surgical Resection

Number:

07-C-0043

Summary:

This study will evaluate how an experimental drug for cancer treatment gets into tumors and normal tissue. This drug, a new method of delivering tumor necrosis factor (TNF), is called TNF-bound colloidal gold, or CYT-6091. TNF is normally produced by cells in the immune system and has also been found to have anti-cancer effects. Doses that might be high enough to shrink tumors cause serious side effects, so researchers have focused on getting TNF directly to the tumor. This study uses microscopic gold particles that have TNF bound or attached to their surface. Attaching the gold molecule to TNF may decrease severity of side effects when TNF is given to humans.

Patients aged 18 and older who do not have bleeding disorders or serious problems of the heart or lungs may be eligible for this study. They will undergo a complete physical and medical history as well as a complete blood count and blood chemistry, urine analysis, pregnancy test, chest X-ray, and electrocardiogram as part of the process to determine.

Patients who are eligible and who have surgery scheduled will be admitted to the hospital. They will get one injection of CYT-6091 at 12, 24, 48, or 72 hours before surgery. A long flexible thin plastic tube (catheter) is used to administer CYT-6091. It is threaded into a large vein in the arm that leads to the heart. After that line is inserted, patients will be given some fluids through it, for 2 to 3 hours before the dose of CYT-6091. Then CYT-6091 will be given for about a minute. Researchers will monitor patients' hearts and breathing. They will also check blood pressure, heart, breathing, and temperature every 15 minutes for 7 or 8 times, and then routinely to watch for any side effects. During surgery, pieces of tumors and pieces of normal tissue near the tumor or incision will be removed for this research study. Taking the extra pieces of normal tissue will not increase the operation time or cause an additional risk. The rest of the tumor will be sent to the laboratory for analysis. After surgery, patients will receive routine care, including pain medications, and get specific information about what to expect after surgery. Six weeks after they are discharged, patients will return to the clinic for a routine visit and then about every 3 to 6 months for 3 years. At each visit, they will have a physical examination and have blood drawn. They may have computed tomography or magnetic resonance imaging scans, if appropriate.

This study is unlikely to have a direct benefit for participants. However, knowledge gained will provide valuable information about how CYT-6091 travels to tumors and normal tissue.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA

Histologically documented evidence of a primary or metastatic malignancy falling into one of the following histologic groups: adenocarcinoma of gastrointestinal (GI) origin, hepatocellular cancer, pancreas, exocrine cancer, pancreas, endocrine cancer, breast cancer, melanoma, peritoneal mesothelioma, and sarcoma, primary adrenal tumors, ovarian cancer, and renal cell carcinoma. The diagnosis will be confirmed by the Laboratory of Pathology, National Cancer Institute.

Primary or metastatic tumor with a clinical indication for surgical resection.

ECOG Performance status less than or equal to 2.

Must be at least 18 years of age. At this time the risk/benefit data is inadequate to predict that the benefit derived would be worth the potential risk of this agent in children.

Expected survival of at least 5 months.

Men and women of child-bearing potential (i.e. women who are premenopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device (IUD), oral contraceptive or double barrier device), and women must have a negative serum and urine pregnancy test 1 week before dosing with this agent. Nursing patients are also excluded. These patients are excluded because the effects of this agent on a fetus or nursing child are unknown.

Must be able and willing to give written informed consent.

Must have had no treatment with cytotoxic agents or treatment with biologic agents within 3 weeks prior to treatment or within 6 weeks prior treatment with nitrosureas. Must have fully recovered from toxicities of any prior treatment with cytotoxic drugs, radiotherapy, surgery, or other anti-cancer modalities (returned to baseline status as noted before most recent treatment) except for those toxicities listed in appendix E.

Patients must have the following clinical laboratory values:

Absolute neutrophil count of greater than or equal to 1,500/mm (3)

Platelets greater than or equal to 100,000/mm (3)

Serum creatinine less than or equal to 2.0 mg/dl

Bilirubin less than or equal to 2.5 mg/dl, ALT, AST less than or equal to 3 times the upper limit of normal, alkaline phosphatase less than or equal to 3 time the upper limit of normal

Hemoglobin greater than or equal to 9.0g/dL (may be corrected by transfusion)

EXCLUSION CRITERIA

Patients with any one of the following criteria will not be eligible for study participation:

Clinical evidence of active bacterial infection (localized chronic infections such as mild acne or tinea pedis are not exclusionary)

Any known bleeding disorder

Presence of any life-threatening illness, such as unstable angina, severe oxygen dependent chronic obstructive pulmonary disease (COPD), end stage live disease

Presence of known brain metastases. Patients with previously treated brain metastases and no evidence of reoccurrence are eligible.

Unwilling or unable to follow protocol requirements

Known active renal disease or renal insufficiency manifest by a serum creatinine of greater than 2.0 mg/dl.

HIV positive as TNF may work through and immune mediated mechanism

Patients on protocols for which they are being evaluated for response

Special Instructions:

Currently Not Provided

Keywords:

Tumor Necrosing Factor

Tumor Angiogenesis

Nanoparticles

Phase 0 Trial

Recruitment Keyword(s):

Metastatic Cancer

Condition(s):

Metastatic Cancer

Investigational Drug(s):

CYT-6091 (Colloidal Gold TNF)

Investigational Device(s):

None

Intervention(s):

Drug: CYT-6091 (Colloidal Gold TNF)

Supporting Site:

National Cancer Institute

Contact(s):

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
Phone: (866) 820-4505
Fax: (301) 451-1927
Electronic Address: ncisbirc@mail.nih.gov

Citation(s):

Kimura K, Taguchi T, Urushizaki I, Ohno R, Abe O, Furue H, Hattori T, Ichihashi H, Inoguchi K, Majima H, et al. Phase I study of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol. 1987;20(3):223-9

Taguchi T. Phase I study of recombinant human tumor necrosis factor (rHu-TNF:PT-050). Cancer Detect Prev. 1988;12(1-6):561-72

Creaven PJ, Plager JE, Dupere S, Huben RP, Takita H, Mittelman A, Proefrock A. Phase I clinical trial of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol. 1987;20(2):137-44.

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