Clinical trial NCT00908791: Proof of Principle Trial to Determine if Nutritional Supplement Conjugated Linoleic Acid (CLA) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
Official title: An in Vivo Proof of Principle Trial to Determine Whether the Nutritional Supplement Conjugated Linoleic Acid (CLA, Clarinol™) Can Modulate the Lipogenic Pathway in Breast Cancer Tissue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Breast Cancer
Keywords: Conjugated Linoleic Acid
Proof of Principle
Lipogenic Pathway
Clarinol
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: Dartmouth College
First posted: 2009-05-27
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Conjugated Linoleic Acid (CLA) is obtained in the human diet by consumption of foods containing ruminant fat. Milk and dairy products have shown the highest amounts of CLA. Clarinol (CLA), is considered a natural supplement and is not regulated by the Food and Drug Administration (FDA). CLA is known to inhibit proliferation of human breast cancer cells and tumors in rodent breast cancer models and reduced Spot 14 (THRSP, S14) and Fatty Acid Synthase (FASN) gene expression in breast cancer cells and tht the two major CLA isomers used in nutritional supplements (C9, t11 and t10, c12) were equipotent in reducing breast cancer cell growth. This study looks at the hypothesis that S14 expression is decreased by CLA and will characterize the major pharmacodynamic (PD) effects of CLA in newly diagnosed Breast cancer patients on Tumor tissue lipogenic pathway. FASN, S14 and Lipoprotein Lipase (LPL), Ki67 and apoptotic index expression will be assessed by quantitative immunohistochemistry (IHC) in initial breast cancer biopsies and compared to that in resected breast tumor tissue after the study subject has been taking CLA for ten to twenty-eight days. Tissue from adjacent breast adipocytes will also be analyzed to determine whether adipose tissue effects can serve as a surrogate marker for those in tumor tissue. A sample of the original biopsy will be compared to the tumor resection sample to determine the levels of CLA in the breast cancer cells.


Eligibility criteria: Inclusion Criteria:

* All study patients must have histologically confirmed invasive adenocarcinoma of the breast. Their breast cancer must be resectable clinical stage I or II breast cancer as defined by the current AJCC TNM Staging System (Greene FL, Page DL, Fleming ID, et al.: editors. AJCC cancer staging manual, 6th edition. New York: Springer; 2002).
* All patients must be able to and give informed consent indicating they are aware of the investigational nature of this treatment, prior to entry into the study.
* All subjects must be Age \>18 years.
* All subject must have adequate hepatic and renal function documented prior to study entry to include: hepatic transaminases (AST or ALT) ≤ 1.5 times the upper limits of normal, total bilirubin ≤ 1.5 times the upper limits of normal, serum creatinine ≤ 1.5 times the upper limit of normal or eCRCl ≥ 60 mL/min.

Exclusion criteria:

* Patients who have received prior or be receiving radiation therapy for their breast cancer will be excluded.
* Patients who have received prior chemotherapy or receiving chemotherapy or hormonal therapy for their breast cancer will not be included.
* Women must be surgically sterilized or post-menopausal or women of childbearing potential must be using an adequate method of contraception. Women of childbearing potential must be using at least one of the following: oral, implanted, injectable contraceptive hormones, or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or have a partner that is sterile (e.g., vasectomy). Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to start of study therapy. Women who are pregnant or breast-feeding and women of childbearing potential not using an adequate method of birth control will be excluded.
* Patients with gastrointestinal abnormalities including: inability to take oral medication, requirement for intravenous alimentation, or prior surgical procedures affecting nutrient /drug absorption will be excluded.
* A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment will be excluded. Significant cardiac disease, including uncontrolled high blood pressure, unstable angina, and congestive heart failure, myocardial infarction within the previous 3 months or serious cardiac arrhythmias will be excluded. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol will be excluded.

Primary outcomes:
measure: Number of Participants With Spot 14 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
timeFrame: Up to 28 days
Secondary outcomes:
measure: Number of Participants With FASN Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
timeFrame: Pre-CLA treatment and up to 2 years Post-CLA treatment
measure: Number of Participants With LPL Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry and Staining Intensities Scored at 0, 1, or 2
timeFrame: Pre-CLA treatment and up to 2 years Post-CLA treatment
measure: Number of Participants With Ki67 Expression Pre and Post CLA as Assessed by Quantitative Immunohistochemistry
timeFrame: Pre-CLA treatment and up to 2 years Post-CLA treatment
measure: Assess Tumor Cell Apoptosis by Immunostaining for Cleaved Caspase 3 Pre and Post CLA
timeFrame: Pre-CLA treatment and up to 2 years Post-CLA treatment
measure: Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9,t11 and t10,c12 Matched to Spot 14 Expression.
timeFrame: Pre-CLA treatment and up to 2 years Post-CLA treatment
measure: Number of Participants With Measurable Concentration of the Circulating Plasma Free CLA Isomers c9t11 and t10c12 Matched to Ki-67 Expression
timeFrame: Pre-CLA treatment and up to 2 years Post-CLA treatment
measure: Safety of Short Term Treatment With 7.5 Gram CLA Per Day.
timeFrame: 2 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center
state: New Hampshire
Study officials:
affiliation: Norris Cotton Cancer Center
name: Burton L Eisenberg, MD
role: PRINCIPAL_INVESTIGATOR
References: