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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03383107
• Other study ID #: 1708018471
• Status: Completed
• Start date: January 22, 2018
• Est. completion date: July 31, 2021

Study information

• Verified date: August 2022
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: July 31, 2021
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Prostate Cancer
• Prostatic Neoplasms

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Varian Medical Systems

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	prospectively collecting blood specimens to assess peripheral immune mediatiors in 4 distinct clinical settings	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)	4 years
Primary	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	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.	4 years
Secondary	microbiome changes associated with different radiation treatments through collection of stool microbiome samples at different time points	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	4 years