Protocol Number: 06-C-0167

Title:

A Phase I Trial of TNF-Bound Colloidal Gold (CYT-6091) by Intravenous Administration in Subjects with Advance Solid Organ Malignancies

Number:

06-C-0167

Summary:

Background:

-Tumor necrosis factor (TNF) has anti-cancer effects, but in doses high enough to shrink tumors it causes serious side effects.

-In studies in laboratory mice, TNF that was attached, or "bound," to microscopic gold particles collected in tumors and destroyed tumor cells with fewer side effects, because the higher TNF levels were only in the tumor and less of the drug was released into the blood.

-Gold-bound TNF (CYT6091) is an experimental drug that has not been given to humans before.

Objectives:

-To determine the highest dose of CYT6091 that can safely be given to patients with solid tumors and to identify the drug's side effects.

-To determine how the drug behaves in the body (how it is used and eliminated) and its effects on tumor tissue.

Eligibility:

-Patients 18 years of age or older with a solid tumor that has spread beyond the primary organ site.

-Patients whose cancer cannot be treated successfully with standard therapies or for which conventional treatment is not available.

Design:

-Patients are admitted to the hospital for approximately 4 days for CYT6091 infusions. The drug is given through a catheter (plastic tube) that is threaded from a large arm vein to the heart. Doses are given 2 weeks apart; two doses are considered one treatment course. Patients whose tumor remains stable or shrinks after the first treatment course may be offered additional courses until their disease progresses or side effects become unacceptable.

-Patients are evaluated throughout the study with tests to determine the size and extent of tumor and the impact of treatment. This includes periodic blood tests, physical examinations, scans and x-rays. Additional blood tests are done for research. After treatment ends, patients are followed with the same evaluations at longer intervals.

-Patients with tumors that are easy to biopsy may be asked to undergo a biopsy to evaluate the amount of CYT6091 in the tumor. A piece of normal tissue next to the tumor is also biopsied. Additional biopsies may be requested in patients who receive additional courses of therapy.

-Up to 60 patients may be enrolled in the study.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Only patients with advanced and/or metastatic, histologically documented solid organ cancers will be included. The diagnosis will be confirmed by the Laboratory of Pathology, National Cancer Institute.

Patients must have a solid tumor which is no longer considered responsive to available conventional modalities or treatments (progressed while receiving any known standard curative or palliative therapy for that disease), or a previously untreated tumor for which no effective standard treatment is available. Patients must have measurable or evaluable metastatic disease.

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 treatment in children.

Expected survival of at least 3 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 or urine pregnancy test 1 week before beginning treatment on this trial. 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 of 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 F.

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.

ALT, AST less than or equal to 1.5 x the upper limit of normal (ALT, AST, less than or equal to 10 x the upper limit in presence of liver metastases).

Bilirubin less than or equal to 2.5 mg/dl.

Prothrombin Time (PT) less than or equal to 1.5x the upper limit of normal.

Hemoglobin greater than or equal to 10.0g/dL (may be corrected by transfusion).

Patients who are greater than 50 years of age or who have a history of cardiovascular disease, must have a normal echocardiogram or thallium stress test with EF greater than or equal to 45%.

Patients who have a history of pulmonary disease must have adequate pulmonary reserve evidenced by FEV1 greater than 30% predicted.

EXCLUSION CRITERIA:

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

Diagnosis of lymphoma or other hematologic malignancy.

Active bacterial or viral infection with systemic manifestations (fever, symptoms, leukocytosis - localized chronic infections such as mild acne or tinea pedis are not exclusionary).

Any known bleeding disorder.

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

Requirement for immediate palliative treatment of any kind including surgery.

Presence of known brain metastases. Patients with previously treated brain metastases and no evidence of recurrence 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 an immune mediated mechanism.

Special Instructions:

Currently Not Provided

Keywords:

Tumor Necrosis Factor

Metastatic Cancer

Cytokine

Maximum Tolerated Dose

Dose Limiting Toxicity

Recruitment Keyword(s):

Solid Tumor

Solid Organ Cancer

Metastatic Solid Organ Cancer

Condition(s):

Advanced Solid Organ Malignancy

Solid Organ Cancer

Investigational Drug(s):

CYT-6091

Investigational Device(s):

None

Intervention(s):

Drug: CYT-6091

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@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.

Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Hariri RJ, Fahey TJ 3rd, Zentella A, Albert JD, et al. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470-4.

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