Clinical Trial: Mistletoe Extract and Gemcitabine for the Treatment of Solid Tumor Cancers

This study is currently recruiting patients.

Sponsored by: National Center for Complementary and Alternative Medicine (NCCAM)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

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.

Condition Treatment or Intervention Phase
Pancreatic Neoplasms
Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Breast Neoplasms
 Drug: Helixor A
Phase I

MedlinePlus related topics:  Breast Cancer;   Cancer;   Colorectal Cancer;   Lung Cancer;   Pancreatic Cancer
Genetics Home Reference related topics:  breast cancer

Study Type: Interventional
Study Design: Treatment, Safety

Official 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

Further Study Details: 

Expected Total Enrollment:  51

Study start: August 2, 2002

Over the past 80 years, plant extracts of the European mistletoe Viscum album L. have been widely used for cancer treatment in European countries. Preclinical data suggest immunostimulatory and other immunomodulatory effects of this plant extract. In clinical practice, mistletoe extracts have been used in cancer patients as sole intervention or as adjunct to conventional cancer therapies. Clinical efficacy in the treatment of cancer is an area of active investigation, with inconclusive results to date due in large part to the use of varying preparations, concentrations, study populations and regimens. Moreover, little is known about the toxicity of mistletoe and the potential for interactions between mistletoe extract and standard chemotherapeutic agents.

Gemcitabine is an FDA-approved antimetabolite chemotherapeutic agent with demonstrated single agent efficacy in the treatment of a wide range of solid tumors. Since the metabolism and pharmacokinetics of gemcitabine are well characterized, it is a chemotherapeutic agent well suited for the study of botanical/drug interactions in cancer therapy.

The goals of this study are to investigate in a two-stage, phase I dose escalation design the effect of a highly purified mistletoe extract on pharmacokinetics pharmacodynamics and safety of gemcitabine, a well characterized chemotherapeutic agent. Pharmacokinetic toxicity profiles of gemcitabine in combination with mistletoe, neutrophil recovery, cytokine gene expression, and serum levels of markers of immune activation will be investigated in approximately 40 - 50 patients with advanced solid tumors. The study aims at establishing a paradigm for the investigation of botanicals used in conjunction with standard cancer chemotherapy in complementary cancer medicine.

Eligibility

Genders Eligible for Study:  Both

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.

Location and Contact Information


Maryland
      National Center for Complementary and Alternative Medicine (NCCAM), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Hostanska K, Hajto T, Spagnoli GC, Fischer J, Lentzen H, Herrmann R. A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells. Nat Immun. 1995 Sep;14(5-6):295-304.

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

Rentea R, Lyon E, Hunter R. Biologic properties of iscador: a Viscum album preparation I. Hyperplasia of the thymic cortex and accelerated regeneration of hematopoietic cells following X-irradiation. Lab Invest. 1981 Jan;44(1):43-8.

Study ID Numbers:  020260; 02-AT-0260
Record last reviewed:  July 15, 2004
Last Updated:  November 23, 2004
Record first received:  August 20, 2002
ClinicalTrials.gov Identifier:  NCT00044161
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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