Protocol Number: 02-AT-0260

Title:

A Phase I Study of the Effect of Mistletoe Extract, a Complementary, Medicine Botanical, on Pharmacokinetics, Pharmacodynamics and Safety of Gemcitabine in Patients with Advanced Solid Tumors

Number:

02-AT-0260

Summary:

This study will examine the safety and effectiveness of the combination of mistletoe extract and gemcitabine in patients with solid tumor cancers. Gemcitabine is approved by the Food and Drug Administration to treat various cancers, including those of the lung, bowel, breast and pancreas. The FDA has approved mistletoe extract for use in cancer treatment studies. Mistletoe extract has been used either alone or together with conventional anti-cancer drugs to treat cancer in tens of thousands of patients in Europe. Data from some studies suggest that this substance may stimulate the immune system and may make cancer patients feel better overall.

Patients 18 years of age or older with pancreatic, colorectal, lung, or breast cancer that cannot be surgically removed, has recurred, or has spread beyond the primary site may be eligible for this study. Patients with lung and pancreatic cancer may be enrolled whether or not they have previously received chemotherapy; patients with breast and colorectal cancer must have received first-line chemotherapy without being cured, before being eligible for this study.

Participants will receive test medications as follows:

- Gemcitabine will be prescribed in a standard regimen as it would be indicated for any cancer patient in an outpatient oncology clinic. Gemcitabine will be administered in 3-week cycles as follows: day 1 of the first week and day 1 of the second week, with no infusion given the third week. The drug is given in 30-minute infusions through a catheter (thin plastic tube) placed in an arm vein.

- Mistletoe extract will be administered as an injection under the skin on the abdomen once a day every day starting with the second gemcitabine infusion. Patients will be taught how to self-administer the injections.

There are two treatment stages. In the first stage, all patients will receive the same dose of gemcitabine. The mistletoe dose will vary, with groups of three patients receiving increasingly higher doses of the extract. In the second stage, the gemcitabine dose will be increased in groups of three patients until side effects are no longer tolerated, at which point the dose will be lowered. The mistletoe dose will not vary for patients enrolled in stage two of the study.

Participants will have the following tests and procedures:

- Blood tests - On the day of the first gemcitabine treatment, blood samples will be drawn before and several hours after the infusion to measure how much of the drug gets into the body and how long it stays in the body. This test will be repeated about 6 to7 weeks after starting mistletoe treatment to see what effect the mistletoe has on the length of time gemcitabine remains in the body. Several times during the study, blood samples will be collected to test immune system functions and to determine whether genes in certain immune system cells become active during treatment.

- Scans and X-ray studies - Imaging studies will be done every 3 treatment cycles (about every 9 weeks) to examine the response of the tumor to treatment.

Sponsoring Institute:

National Center for Complementary and Alternative Medicine (NCCAM)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA

Historically confirmed cancer of the pancreas, colorectal cancer, non-small cell lung cancer or breast cancer that is either metastatic, or unresectable locally advanced or recurrent disease.

Patients with breast and colorectal cancer should have been treated and failed therapy with first line agents such anthracycline/alkylating agent based chemotherapy (breast cancer) or 5FU-based chemotherapy (colorectal cancer) prior to enrollment.

Chemotherapy-naive patients with lung and pancreatic cancer may be enrolled.

ECOG performance status 0-1.

Bilirubin less than or equal to 2.0.

Hematologic function: Adequate bone marrow function defined as peripheral absolute neutrophil count greater than or equal to 1,500/microliter, and a platelet count greater than or equal to 100,000 microliter.

Age greater than or equal to 18 years at study enrollment.

Recovered from treatment-related toxicity of prior chemotherapy, radiation therapy or surgery, according to the clinical the judgment of the Principal or Associate Investigators.

Last investigational agent treatment received at least 30 days prior to study entry.

EXCLUSION CRITERIA

Glucocorticoseroid therapy within the last 30 days prior to study entry.

Prior chemotherapy within last 30 days prior to study entry.

Prior chemotherapy with gemcitabine.

Prior use of mistletoe.

Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient's ability to tolerate the study regimen or are likely to interfere with the study procedures or results.

Serum creatinine greater than 2.5 mg/dl.

Current use of other investigational agents.

Pregnant or breast-feeding women are excluded because the study regimen may be harmful to the developing fetus or nursing child.

HIV antibody positivity.

Clinical or radiographic evidence of CNS metastasis.

Special Instructions: Currently Not Provided

Keywords:

Advanced Cancer

Cytokines

Immunostimulation

Tumor Response

Toxicity

Recruitment Keywords:

Cancer

Pancreatic Cancer

Breast Cancer

Colorectal Cancer

Lung Cancer

Solid Tumor

Conditions:

Pancreatic Neoplasms

Colorectal Neoplasms

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Investigational Drug(s):

Helixor A

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Hostanska K, A plant lectin derived from Viscum album induces cytokine gene expression andprotein production in cultures of human peripheral blood mononuclear cellsNat Immun 1995 Sep;14(5-6):295-304PMID: 8933823

Stein G, Berg PA Non-lectin component in a fermented extract from Viscum album L grown on pinesinduces proliferation of lymphocytes from healthy and allergic individuals invitroEur J Clin Pharmacol 1994;47(1):33-8PMID: 7988621

Rentea R, Lyon E, Hunter R Biologic properties of iscador: a Viscum album preparation I Hyperplasia of thethymic cortex and accelerated regeneration of hematopoietic cells followingX-irradiationLab Invest 1981 Jan;44(1):43-8PMID: 7453129

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