Effect of Radiotherapy Variables on Circulating Effectors of Immune Response and Local Microbiome

• ClinicalTrials.gov Identifier: NCT03383107
• Recruitment Status: Completed
• First Posted: December 26, 2017
• Last Update Posted: August 12, 2022
• Sponsor: Weill Medical College of Cornell University
• Collaborator: Varian Medical Systems
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

Brief Summary:

Exposure to radiation can impact immune cells that are present in the blood, such as lymphocytes. It is hypothesized that larger radiation fields and/or longer courses of radiation, result in greater decrease in immune cells. To test this hypothesis, investigators will take blood samples from subjects undergoing two different standard of care radiation regimens for prostate cancer, and subjects undergoing two different standard of care regimens for breast cancer.

Condition or disease
Breast Cancer; Prostate Cancer

Detailed Description:

The study prospectively collects blood specimens for assessment of peripheral immune mediators in 4 distinct clinical settings of standard radiotherapy. In addition to collecting blood specimens, the study will also collect physical and dosimetric information of treatment such as total dose, number of treatments, and/or size of the radiation targe, as these will allow the investigators to study the impact of radiation variables on the immune system. Stool specimens will be collected at baseline, end of radiation therapy and during the follow up visit to detect microbiome changes associated with different radiation treatment at various time points. Humans are colonized by commensal bacteria, which outnumber human cells. These normal bacteria colonize mucosal surfaces and play a critical role in immunity. It is hypothesized that the underlying microbiota may also undergo changes in composition that correspond to the regimen of radiation that is utilized. By collecting stool specimens, investigators will be able to study microbial changes and how these changes correlate with alteration in immune mediators (i.e., lymphocytes, cytokines) present in blood samples before, during and after radiation; and explore the association between these parameters and type of radiation received.

Study Design

• Study Type: Observational
• Actual Enrollment: 66 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Effect of Radiotherapy Variables on Circulating Effectors of Immune Response and Local Microbiome
• Actual Study Start Date: January 22, 2018
• Actual Primary Completion Date: July 31, 2021
• Actual Study Completion Date: July 31, 2021

Groups and Cohorts

Group/Cohort
Cohort 1a - Prostate Cancer; Standard fractionation RT to 81 Gy in 45 fx over 9 weeks
Cohort 1b - Prostate Cancer; Hypofractionated RT to 36.25 Gy in 5 fx over 1-2 weeks
Cohort 2a - Breast cancer; Standard fractionation breast and nodal RT to 50 Gy in 25 fx over 5 weeks
Cohort 2b - Breast Cancer (Partial Breast ); Partial breast RT to 30 Gy in 5 fx over 2 weeks

Outcome Measures

Primary Outcome Measures :

1. prospectively collecting blood specimens to assess peripheral immune mediatiors in 4 distinct clinical settings [ Time Frame: 4 years ]
   prospectively collect collect physical and dosimetric information of treatment and sequential blood samples for assessment of peripheral immune mediators in 4 distinct clinical settings of standard radiotherapy (2 for breast and 2 for prostate cancer)
2. distribution and frequency of peripheral immune mediators before, during and after radiotherapy will be assessed from blood samples that are collected at various time points [ Time Frame: 4 years ]
   To characterize the distribution and frequency of peripheral immune mediators before, during and after radiotherapy in each of the 4 subsets of the prospective trial.

Secondary Outcome Measures :

1. microbiome changes associated with different radiation treatments through collection of stool microbiome samples at different time points [ Time Frame: 4 years ]
   explore microbiome changes associated with different radiation treatments through collection of stool microbiome samples at baseline, at the end of radiation therapy, and during follow up after completion of Radiotherapy

Biospecimen Retention:   Samples Without DNA

Blood specimens will be collected prospectively from consented patients at baseline, during radiation therapy, at completion of radiation therapy and during 3-4 month follow up visit.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Men with biopsy-proven, non-metastatic prostate adenocarcinoma, meeting the inclusion/exclusion criteria below, and electing to undergo definitive radiation treatment, will be eligible for participation.

Women with biopsy-proven, non-metastatic invasive or in situ breast cancer meeting the inclusion/exclusion criteria below will be eligible for participation.

Criteria

Cohort 1a and b: Prostate cancer subjects undergoing 9 week radiation

Inclusion criteria:

• Biopsy-proven diagnosis of prostate adenocarcinoma
• Age ≥ 18

Exclusion criteria:

• History of prior pelvic radiation (external beam or brachytherapy)
• Prior or concurrent lymphomatous/hematogenous malignancy, or history of prior/concurrent invasive malignancy during the past 5 years
• History of hormone therapy such as LHRH agonists (gosrelin, leuprolide), anti-androgens (flutamide, bicalutamide), surgical castration (orchiectomy)
• History of irritable bowel disease
• Evidence of lymph node involvement or metastatic disease

Cohort 2a : Breast cancer subjects undergoing standard fractionation RT of 5 weeks

Inclusion criteria:

• Biopsy-proven diagnosis of invasive breast cancer, s/p breast surgery to negative margins, and requiring adjuvant breast and nodal RT
• Age ≥ 18

Exclusion criteria:

• History of prior radiation therapy to the ipsilateral breast
• Prior or concurrent lymphomatous/hematogenous malignancy, or history of prior/concurrent invasive malignancy during the past 5 years
• < 1 month from completion of chemotherapy to start of RT
• Evidence of metastatic disease

Cohort 2b: Breast cancer subjects undergoing PBI

Inclusion criteria:

• Post-menopausal women defined as either 1) at least 2 years without menstrual period or 2) or patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with FSH confirmation of post-menopausal status.
• Post-segmental mastectomy with negative margins
• If bilateral, pT1 breast cancer, excised with negative margins AND/OR
• pTis excised with negative margins
• Clinically N0 or pN0 or sentinel node negative
• Diagnosis of ductal carcinoma in situ DCIS, limited to <2cm size of DCIS and to lesions of low or intermediate grade, excised (or re-excised) with final negative margins ( no DCIS on inked margins).
• Age ≥ 18

Exclusion criteria:

• History of prior radiation therapy to the ipsilateral breast
• Presence of a proportion of DCIS in the core biopsy specimen which is compatible with extensive intraductal component (EIC).
• < 1 month from completion of chemotherapy to start of RT
• Evidence of metastatic disease

Contacts and Locations

Locations

United States, New York

Weill Cornell Medical College

New York, New York, United States, 10065

Sponsors and Collaborators

Weill Medical College of Cornell University

Varian Medical Systems

Investigators

• Principal Investigator: Silvia Formenti, M.D.; Weill Cornell Medicine - New York Presbyterian Hospital

More Information

Publications:

Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013 Feb 20;105(4):256-65. doi: 10.1093/jnci/djs629. Epub 2013 Jan 4.

Formenti SC, Demaria S. Radiation therapy to convert the tumor into an in situ vaccine. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):879-80. doi: 10.1016/j.ijrobp.2012.06.020. No abstract available.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03383107
• Other Study ID Numbers: 1708018471
• First Posted: December 26, 2017
• Last Update Posted: August 12, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases