Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

SAbR Induced Innate Immunity in Urothelial Carcinoma, Melanoma, and Cervical Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02986867
Recruitment Status : Completed
First Posted : December 8, 2016
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Brief Summary:
The study is an exploratory prospective, single center study with correlative endpoints. The study will investigate the association of tumor cGAS STING signaling with SAbR. Tumor core biopsies will be processed and analyzed as described above. Medical records electronic medical records will be used to collect demographic and medical information and imaging studies.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Melanoma Cervical Carcinoma in Situ Radiation: SAbR Treatment of Lesions Not Applicable

Detailed Description:

Within 2 weeks of planned SAbR, patients will have a core biopsy of the lesion to receive SAbR. Laboratory values will be obtained prior to biopsy. Once the laboratory values are found to be within the safe margin for biopsy, multiple (approximately 5) core biopsies will be obtained with an 18-guage or 19-gauge needle under CT or US guidance. Tissue will be snap frozen with liquid nitrogen and immediately transferred to the laboratory of Dr. Zhijian "James" Chen, PhD, Professor, Department of Molecular Biology.

SAbR will be administered as per the guidelines of UTSW with a single 24-27Gy or three 10-14 Gy/fraction fractions totaling 33-48Gy. Lesions receiving SAbR will be called "radiated" lesions. Prior irradiated lesions will be excluded. SABR will be administered within 2 weeks of the study initial core biopsy. The SAbR dose and fractionation scheme is generated to deliver a potent dose to ablate the targeted lesions and at the same time maximize an immune response. Since multiple studies have shown an influx of lymphocytes and monocytes after tumor irradiation and since these cells play a critical role in antigen presentation and initiation of an adaptive immune response, multiple fraction irradiation which would kill these infiltrating immunocytes, is discouraged. Therefore a single fraction or a three fraction treatment regimen is recommended, and a single fraction treatment is preferred over three fractions. Due to normal organ toxicity and limits of dose constraints, sometimes a three fraction treatment must be undertaken and in those cases it is recommended that the treatment course is completed within 7-10 days-preferably 5 business days. Radiation dose-immune response studies have shown a linear increase in immune response with increased dose per fraction of radiation without demonstration of a plateau. Two studies comparing 15Gy x 1 vs 5Gy x3, and 20Gy x1 vs 5Gy x4 have shown a superior immune response generated by the single fraction radiation. Clinical experience with oligometastatic patients treated at 1-5 sites of disease has also showed an increase in progression-free survival with the increasing radiation dose per fraction. A dose of less than 7.5 Gy per fraction has demonstrated lower induction of systemic IFN-γ producing cells, and a previous phase II study of mRCC patients treated with HD IL-2 and singe fraction of 8Gy irradiation to a single lesion did not show an overall improvement in response rate. Therefore 8Gy per fraction is the lowest permitted dose for this study and can be used only when administering the three fraction regimen as described in the prescription dose table below. Investigators will have discretion in choosing from either of the biologically equivalent dose levels using one or three fractions, although a single fraction is preferred over three fraction treatments. Treating physician will have further discretion in selecting the number and location of sites to treat if multiple sites of disease are present. Maximum number of lesions treated is deemed as feasible per the treating radiation oncologist. However, for the purposes of this protocol, only a single site will be studied and must be safely amenable to repeat core biopsy. Thus, the single site for the study will be either in subcutaneous tissues, nodes, isolated masses or liver. The gross target/tumor volume--GTV should be at least 2 cm3 in size, corresponding to roughly a 1.5 cm diameter tumor. This is to ensure that adequate tumor volume for therapy and for biopsy and therefore adequate tumor cells roughly 108 -109 cells/cm3 are killed for antigen presentation. Treating physicians should choose their dose based on established planning guidelines at their center including their ability to respect normal tissue tolerance.

Within 24 + 6 hours of the first SAbR, a second core biopsy of the "target" irradiated lesion will be performed identically to the first biopsy.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: SAbR-Induced Innate Immunity in Urothelial Carcinoma, Melanoma, and Cervical Carcinoma
Actual Study Start Date : June 13, 2017
Actual Primary Completion Date : March 7, 2018
Actual Study Completion Date : March 7, 2018


Arm Intervention/treatment
Experimental: SAbR
SAbR treatment of lesions
Radiation: SAbR Treatment of Lesions
SAbR will be administered as per the guidelines of UTSW with a single 24-27Gy or three 10-14 Gy/fraction fractions totaling 33-48Gy. Lesions receiving SAbR will be called "radiated" lesions.




Primary Outcome Measures :
  1. Comparison of immune checkpoint treated tumors [ Time Frame: 36 months ]
    Compare cGAMP levels, interferon response gene expression and phospho-STING in tumors of immune checkpoint treated patients.

  2. SAbR effects on cGAMP in tumors [ Time Frame: 36 months ]
    Number of participants with SAbRrelated tumor changes indicated by cGAMP in comparison to Baseline.

  3. SAbR effects on interferon response in tumors [ Time Frame: 36 months ]
    Number of participants with SAbRrelated tumor changes indicated by interferon response mRNAs in comparison to Baseline.

  4. SAbR effects on phosphor-STING in tumors [ Time Frame: 36 months ]
    Number of participants with SAbRrelated tumor changes indicated by phospho-STING in comparison to Baseline.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Histologic diagnosis of advanced/metastatic urothelial carcinoma, melanoma, or cervical carcinoma.
  • Planned treated with SAbR.
  • Age greater than or equal to 18 years.
  • Lesion to receive SAbR safely accessible for core biopsy—mass >1.5cm diameter and located in node, liver, or soft tissues.
  • Hgb >10g/dL before or after transfusion.
  • Platelets >50,000/L
  • INR <1.5
  • If contrast enhanced CT needed to locate the lesion for core biopsy, then derived creatinine clearance >30cc/min
  • Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

  • Prior radiation therapy to target lesion.
  • Target lesion not safely accessible for core biopsies.

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): NCT02986867


Locations
Layout table for location information
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75063
Sponsors and Collaborators
University of Texas Southwestern Medical Center

Layout table for additonal information
Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT02986867     History of Changes
Other Study ID Numbers: STU 092016-055
First Posted: December 8, 2016    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Melanoma
Carcinoma, Transitional Cell
Carcinoma in Situ
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas