Protocol Number: 04-C-0218

Title:

A Phase I Study of 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG) with Evaluation of HSP-90 Client Proteins in Patients with Solid Tumors and Lymphomas

Number:

04-C-0218

Summary:

This study will test the safety of an experimental drug, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in patients with solid tumors or lymphomas. It will determine how much 17-DMAG can be given safely and examine how the body responds to the drug. 17-DMAG has shown some anti-cancer effects against tumors in laboratory tests and in animal studies. It has not previously been tested in humans.

Patients 18 years of age and older with a solid tumor cancer or lymphoma for which effective standard treatments are not available may be eligible for this study. Upon enrollment, participants are evaluated with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG) and chest X-ray, diagnostic imaging studies (CT or MRI) to assess the extent of the cancer. In addition, patients undergo the following tests and procedures:

-17-DMAG treatment - 17-DMAG doses are infused through a vein twice a week for 4 weeks, unless too many side effects develop. Each infusion lasts about 1 hour. Treatment may continue beyond 4 weeks in patients whose tumor does not grow and who do not experience severe side effects. After 8 weeks of treatment, the patient's response to the drug is evaluated with a physical examination, scans, and X-rays.

-Blood studies - Blood work includes the following:

2 tablespoons of blood is drawn twice a week (before each drug dose) to assess how kidney, liver, bone marrow, and clotting mechanisms are functioning.

13 tablespoons of blood is drawn twice during the first 4 weeks of treatment to look for drug effects in the blood.

On the first day of 17-DMAG treatment, 1 to 2 teaspoons of blood is drawn before the drug infusion, after the infusion is finished, and another 10 times over the next 48 hours to examine how the body breaks down and eliminates the drug.

-24-hour urine collection - On the first day of 17-DMAG treatment, patients collect all their urine for 24 hours after the drug infusion to study how the body breaks down and eliminates the drug.

-Imaging studies - X-rays and scans are done to evaluate the size and extent of tumor.

-Tumor biopsy - If it can be done safely, a small piece of tumor is surgically removed before treatment starts and again during the first week of treatment and the fourth week of treatment to examine the effects of 17-DMAG on the tumor.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Targeted Drug

Novel Target

Proteomics

Molecular Endpoints

Pharmacokinetics

Recruitment Keyword(s):

Cancer

Lymphoma

Solid Tumor

Condition(s):

Neoplasms

Lymphoma

Investigational Drug(s):

17-DMAG

Investigational Device(s):

None

Interventions:

Drug: 17-DMAG

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Uehara Y, Murakami Y, Sugimoto Y, Mizuno S. Mechanism of reversion of Rous sarcoma virus transformation by herbimycin A: reduction of total phosphotyrosine levels due to reduced kinase activity and increased turnover of p60v-src1. Cancer Res. 1989 Feb 15;49(4):780-5.

June CH, Fletcher MC, Ledbetter JA, Schieven GL, Siegel JN, Phillips AF, Samelson LE. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722-6.

Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8324-8.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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