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Trial record 10 of 24 for:    Porphyrins

Evaluation of Pathway Modulation by Raf, MEK, & Kinase Inhibitors

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ClinicalTrials.gov Identifier: NCT03176485
Recruitment Status : Completed
First Posted : June 5, 2017
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
University of Arizona

Brief Summary:

This is a pilot study designed to evaluate the cutaneous effect of systemic inhibition of the tyrosine kinase pathway in the presence or absence of solar simulated light exposure.

A maximum of 45 subjects will be accrued into the overall study we anticipate approximately 25 patients in the Raf inhibitor group and 10 patients each into the Tyrosine Kinase and MEK inhibitor arms of the study.


Condition or disease Intervention/treatment Phase
Metastatic Cancer Melanoma Colon Cancer Differentiated Thyroid Cancer Hepatocellular Carcinoma Renal Cell Carcinoma Metastatic Melanoma HCC Metastatic Colon Cancer Other: Solar Simulator Not Applicable

Detailed Description:

The study will evaluate the modulatory effect of systemic Raf inhibition in the MEK/ERK and PI3 /Akt/mTOR pathways in patients undergoing targeted therapy for metastatic disease.

Changes in relevant proteins will be evaluated using a combined protein expression methodology that in includes immunohistochemistry (IHC) and reverse phase protein microarray (RPPA) technology.

The primary endpoint of this study will be assessed in normal skin and skin acutely exposed to solar simulated light


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Pilot Study to Evaluate the Signaling Pathway Modulation Demonstrated by Raf, MEK, and Kinase Inhibitors In Human Skin With or Without Solar Simulated Light
Actual Study Start Date : October 17, 2014
Actual Primary Completion Date : November 1, 2018
Actual Study Completion Date : November 1, 2018


Arm Intervention/treatment
Experimental: ArmA: With Solar Simulated Light Exposure Other: Solar Simulator
A Multiport UV Solar Simulator Model 600 (Solar Light Co., Inc., Philadelphia, PA) will be used to administer Solar Simulated Light (SSL) exposures to formerly unexposed buttock skin.The device is equipped with six 8mm liquid light guides (LLG), allowing for 6 simultaneously conducted exposures.A large 3x2 endplate places the LLGs several centimeters apart and is specifically designed for Sun Protection Factor (SPF) and photo patch testing. The dose of emission from each LLG can be precisely regulated and the spectrum of emission can be limited to UVA (320-390 nm) or UVB+UVA (290-390 nm). The operator can select between UVA only and a combined Ultraviolet-A (UVA)/ Ultraviolet-B (UVB) spectrum by placement of an optical filter. The spectral output (indicated below) follows the distribution of sunlight from 290 to 390 nm.
Other Name: Multiport UV Solar Simulator Model 60

Experimental: ArmB: With Solar Simulated Light Exposure (Vemurafenib/Dabraf)
Subjects in this study arm undergo the same procedures as Arm A, with the addition of a blood test for the presence of porphyrins
Other: Solar Simulator
A Multiport UV Solar Simulator Model 600 (Solar Light Co., Inc., Philadelphia, PA) will be used to administer Solar Simulated Light (SSL) exposures to formerly unexposed buttock skin.The device is equipped with six 8mm liquid light guides (LLG), allowing for 6 simultaneously conducted exposures.A large 3x2 endplate places the LLGs several centimeters apart and is specifically designed for Sun Protection Factor (SPF) and photo patch testing. The dose of emission from each LLG can be precisely regulated and the spectrum of emission can be limited to UVA (320-390 nm) or UVB+UVA (290-390 nm). The operator can select between UVA only and a combined Ultraviolet-A (UVA)/ Ultraviolet-B (UVB) spectrum by placement of an optical filter. The spectral output (indicated below) follows the distribution of sunlight from 290 to 390 nm.
Other Name: Multiport UV Solar Simulator Model 60

No Intervention: ArmC: Without Solar Simulated Light Exposure



Primary Outcome Measures :
  1. Modulatory effect of systemic Raf inhibition in the MEK/Erk and PI3 /AKT/mTOR pathways in patients undergoing targeted therapy for metastatic disease [ Time Frame: 2 months ]
    The primary endpoint of the study is to evaluate the modulatory effect of systemic Raf inhibition in the MEK/Erk and PI3 /AKT/mTOR pathways in patients undergoing targeted therapy for metastatic disease. Changes in relevant proteins will be evaluated using a combined protein expression methodology that in includes immunohistochemistry (IHC) and reverse phase protein microarray (RPPA) technology. The primary endpoint of this study will be assessed in normal skin and skin acutely exposed to solar simulated light.


Secondary Outcome Measures :
  1. Downstream modulation of direct Ras and MEK inhibition in human keratinocytes and melanocytes following acute solar simulated light exposure in the presence of metastatic disease treatment with Tyrosine kinase and MEK inhibitors. [ Time Frame: 2 months ]
    The modulatory effect will be evaluated using IHC and RPPA technology.

  2. Modulatory effect of systemic Raf inhibition in the MEK/Erk and PI3 /AKT/mTOR pathways in eligible melanocytic nevi. [ Time Frame: 2 months ]
  3. Correlate the type and severity of cutaneous squamous cell carcinoma development in patients treated with BRaf inhibitors and the modulatory profile identified in the proposed primary endpoint. [ Time Frame: 2 months ]
  4. Safety of performing solar simulated light studies in patients undergoing Ras inhibition for metastatic disease. [ Time Frame: 2 months ]
  5. Modulatory effect of Ras inhibition in Epidermal Growth Factor Receptor (EGFR) and Activating Protein-1 (AP1) signaling pathways (IHC and RPPA). [ Time Frame: 2 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have not yet initiated but plan to undergo dosing with a Tyrosine Kinase inhibitor (TKI) or Raf inhibitor, either alone or with a MEK inhibitor, for treatment of metastatic melanoma, colon cancer, hepatic cell carcinoma, or thyroid cancer.
  • Individuals with normal skin and Fitzpatrick skin type II, III or IV.
  • Individuals who are willing to limit sun exposure to the body during the study period, and who agree to wear protective clothing and SPF 50 broad spectrum sunscreen or sunblock on exposed skin when they are outdoors.
  • Individuals who have the ability to understand and willingness to sign an informed consent before initiation of study procedures, after the nature of the study is explained to them and they have asked any questions.
  • Individuals with a Karnofsky Performance Status of at least 80%.

Exclusion Criteria:

  • Individuals with any inflammation or irritation of the skin at the test area (buttocks), or any skin conditions felt by the study physician to contraindicate enrollment.
  • Individuals with a history of any skin cancer, melanocytic lesions, actinic keratoses or actinic damage in the test area are ineligible. History of such conditions at a body site other than the test area is not exclusionary if in the opinion of the study physician it will not pose a risk to the subject.
  • Individuals who are immunosuppressed by virtue of medication or disease, as determined by the examining study physician. This includes AIDS patients and subjects taking oral steroids.
  • Individuals with active infection, psychiatric illness, or other situations that in the opinion of the study physician limit compliance or interfere with the study regimen.
  • Individuals with a history of photosensitive diseases including, but not limited to, Lupus Erythematosus, pseudoporphyria, or other diseases that in the opinion of the study physician would pose a risk to the subject or interfere with the study.
  • Individuals who have used photosensitizing drugs within the last 30 days prior to study enrollment, or who will be using a photosensitizing drug during the time of the study.
  • Individuals who have used any topical medication other than emollients on the test area within 30 days prior to study enrollment.
  • Individuals who have used retinoids, steroids, 5-fluorouracil, Levulan, Vaniqua (eflornithine), Solaraze, or Imiquimod (Aldara®) anywhere on the body within 30 days prior to enrollment.
  • Individuals must not take mega-doses of vitamins. Mega-doses are defined as more than 5 capsules of standard multivitamins daily or more than the Tolerable Upper Intake Levels of Vitamins, as defined by the Institute of Medicine, National Academy of Sciences. Such vitamin therapy must be discontinued at least 30 days prior to study entry.
  • Individuals with a history of natural or artificial sun exposure to the buttocks within 30 days of study participation.
  • Individuals with Fitzpatrick skin type I
  • Individuals with Fitzpatrick skin type V or VI
  • Individuals enrolled in or who plan to enroll in a clinical intervention trial. There must be a 30-day period between completing a previous study and enrolling in this study. The Principal Investigator will have the option to consider an exception for patients on drugs of interest for the purpose of this study.
  • Individuals with a known allergy to lidocaine.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03176485


Locations
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United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
Sponsors and Collaborators
University of Arizona
Investigators
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Principal Investigator: Clara Curiel-Lewandroski University of Arizona

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Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT03176485     History of Changes
Other Study ID Numbers: 1409505107
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Arizona:
metastatic
melanoma
cancer
colon
thyroid
Differentiated
Hepatocellular Carcinoma
HCC
RCC
Renal Cell Carcinoma

Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Hepatocellular
Colonic Neoplasms
Carcinoma, Renal Cell
Thyroid Neoplasms
Neoplasm Metastasis
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms