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A Molecular Pharmacodynamic Dose-titration Trial of Conjugated Linoleic Acid (CLA; Clarinol®) in Patients With Advanced Solid Tumors

This study has suspended participant recruitment.
(Administrative suspension. PI/grant holder transferred to new institution.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00951158
First received: August 3, 2009
Last updated: March 16, 2012
Last verified: March 2012
  Purpose

It has become apparent that many cancers depend on specific fats (lipids) for their continued growth. Conjugated linoleic acid (CLA) is a safe, popular, and well-tolerated dietary supplement that promotes weight loss and loss of fat. CLA was recently shown to block the metabolism (uptake and production) of lipids required for growth of some cancers, resulting in killing of cancer cells. The investigators will conduct a clinical trial to test whether oral CLA blocks metabolism of lipids in patients with advanced cancers. Since the dose of CLA that may do this is not yet known, the investigators will start at a dose of CLA known to be tolerable and effective for weight loss. If this dose does not block lipid metabolism, the investigators will test higher doses in successive groups of patients until the investigators identify an effective dose, unless the investigators find that these higher doses cannot be tolerated. In order to verify that CLA is absorbed, it is necessary to measure CLA levels in blood before and after doses are given. Likewise, in order to verify that CLA blocks lipid metabolism, the investigators will need to obtain small samples of abdominal fat (and, in some patients, samples of tumors).


Condition Intervention Phase
Advanced Solid Tumors
Dietary Supplement: Conjugated Linoleic Acid
Drug: Conjugated Linoleic Acid
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Molecular Pharmacodynamic Dose-titration Trial of Conjugated Linoleic Acid (CLA; Clarinol®) in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • To define a tolerable dose of oral CLA, given on a daily schedule, that maximally inhibits S14 expression in adipocytes of patients with advanced solid tumors. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To quantify the effects of CLA on S14 expression in tumor tissue, at its recommended phase II dose [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To quantify effects of CLA on expression of lipogenic enzymes regulated by S14, lipoprotein lipase, and phospho-akt in adipocytes (and tumor tissue). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To quantify effects of CLA on expression of biomarkers for cellular proliferation, S/G2 phases of cell cycle, and apoptosis in tumor tissue. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To define the plasma pharmacokinetics of CLA in patients with advanced cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To obtain data on the safety and tolerability of CLA given orally, on a daily schedule to patients with advanced cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To document ant tumor activity of CLA, if observed, in this population. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: March 2010
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: Conjugated Linoleic Acid

    This is a open-label dose-titration trial of CLA in patients with advanced, refractory malignancies. The dose a participant receives is dependent upon the cohort to with the patient is assigned.

    CLA will be given as oral soft gels, once daily, with pharmacokinetic sampling and biopsies (pretreatment and on day 15). Doses will be escalated by patient cohorts, using an accelerated titration design (single-patient cohorts) with expansion to conventional cohort sizes (3-6 patients) once either inhibition of S14 expression or clinical toxicity is observed. Subjects with stable or responsive disease and who tolerate treatment may continue on CLA until the time of disease progression.

    Other Names:
    • CLA
    • Clarinol
    Drug: Conjugated Linoleic Acid
    Phase I Dose Escalation Study
    Other Name: Clarinol, CLA
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

A subject is eligible for inclusion in this study only if all of the following criteria apply:

  1. Written informed consent.
  2. Age 18 years or more.
  3. Performance status of 0, 1, or 2 on the Eastern Co-operative Oncology Group (ECOG) Scale.
  4. A predicted life expectancy of at least 3 months, in the estimation of the investigator.
  5. Subjects with histologically or cytologically confirmed advanced solid tumors, who have failed conventional therapy for their tumor type or have a tumor type for which no standard effective therapy exists.
  6. At least 4 weeks since last chemotherapy, radiotherapy, biologic therapy or surgery. Subjects must be free of post-treatment side effects. No concurrent chemotherapy, biologic therapy or radiotherapy is allowed.
  7. Hematological/clinical chemistry criteria of:

    Hemoglobin ≥ 9.0 g/dL WBC ≥ 3,500/mm3 [≥ 3.5 x 109/L] Neutrophils ≥ 1,500/mm3 [≥ 1.5 x 109/L] Platelets ≥ 100,000/mm3 [≥ 100.0 x 109/L] Calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault Formula.

  8. Serum bilirubin < 2.0 mg/dL (34 µmol/L)
  9. SGOT/AST, SGPT/ALT and alkaline phosphatase < 2 times the upper limit of normal if liver metastases cannot be visualized by abdominal computed tomography (CT) or magnetic resonance imaging (MRI scan). If liver metastases are present, subjects with < 5 times the upper limit of normal are eligible to participate.
  10. Once the RP2D is established, additional patients enrolled at the expanded dose cohort must have tumor that is accessible to two serial biopsies and that is documented (by IHC or RT-PCR) to express S14.

Exclusion Criteria

A subject is ineligible if any of the following criteria apply:

  1. Cancer cachexia, defined by the combination of: unintentional weight loss ≥10%, low

    caloric intake (≤ 1500 kcal/day), and systemic inflammation (C-reactive protein ≥ 10mg/L).[52]

  2. Type II diabetes mellitus
  3. Women who are pregnant or lactating, or women subjects of childbearing potential who refuse to practice adequate contraception. (oral contraceptives or IUD; double barrier such as diaphragm plus spermicide; vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner of that female). Childbearing potential is defined as women who are not surgically sterilized (i.e. have not had a hysterectomy, bilateral oophorectomy [ovariectomy], or bilateral tubal ligation) or post-menopausal (i.e., documented absence of menses for one year prior to entry into the study).
  4. Men unwilling to abstain from sex or use effective contraception during the study.
  5. Subjects with uncontrolled emesis, regardless of etiology.
  6. Active infection, or seropositivity for HIV or Hepatitis B/C.
  7. Subjects with clinical evidence of any gastrointestinal (GI) conditions (i.e., removal of a portion of the stomach, recent GI obstruction or GI neuropathy) or subjects taking drugs that would alter GI absorption or motility (e.g., cisapride).
  8. Intercurrent severe medical problems, which would significantly limit full compliance with the study or expose the subject to unnecessary risk.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00951158

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Raymond P Perez, MD University of Kansas
  More Information

Additional Information:
No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00951158     History of Changes
Other Study ID Numbers: D0914, R21CA131820-01A2
Study First Received: August 3, 2009
Last Updated: March 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
Conjugated Linoleic Acid
Clarinol
S14 Expression

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 27, 2014