Three Fraction Radiation to Induce Immuno-Oncologic Response (TRIO)
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|ClinicalTrials.gov Identifier: NCT03978663|
Recruitment Status : Recruiting
First Posted : June 7, 2019
Last Update Posted : August 14, 2020
|Condition or disease||Intervention/treatment||Phase|
|High-Risk Cancer Locally Advanced Breast Cancer||Radiation: Neoadjuvant radiotherapy||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluating the Use of Stereotactic Radiation Therapy Prior to Neoadjuvant Chemotherapy for High-risk Breast Carcinoma (a SIGNAL Series Clinical Trial): Three Fraction Radiation to Induce Immuno-Oncologic Response (TRIO Trial)|
|Estimated Study Start Date :||August 2020|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2023|
Experimental: Neoadjuvant radiotherapy
3 doses of stereotactic radiotherapy administered prior to neoadjuvant chemotherapy in high-risk breast cancers.
Radiation: Neoadjuvant radiotherapy
Neoadjuvant radiation therapy delivered to a portion of the index tumour for high-risk breast carcinoma for immune priming prior to neoadjuvant radiation
- Pathologic complete response [ Time Frame: Measured at time of surgery, typically 6 months after enrollment in trial. ]Pathologic complete response rates after neoadjuvant radiotherapy and chemotherapy will be evaluated.
- Response rates in the primary post chemotherapy by imaging [ Time Frame: Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery, typically 6 months after enrollment in trial. ]Response rates in the primary post chemotherapy by MRI +/- PET scan compared to pre-neoadjuvant radiation imaging
- Response rates in the axillary nodes post chemotherapy by imaging and pathology [ Time Frame: Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery (imaging) and at time of surgery, typically 6 months after enrollment in trial. ]Absence of any invasive breast cancer cells in any tissue at time of surgery
- Immune priming [ Time Frame: Measured 14-20 days after the last dose of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy. ]Immune priming as measured by amount of tumour infiltrating lymphocytes (CD8) into tumour specimen, as well as the expression of immune markers (PDL1, Fox3) and immune panel in blood (CD4, CD8, neutrophil, and macrophage counts). Angiogenesis will be examined using the CD31 or VEGF-a cell markers, proliferation will be examined using the Ki67 marker, hypoxia will be examined using the Carbonic Anhydrase 9 (CAH IX), or HIF1/HIF2 markers, apoptosis will be examined using the Caspase-3, or Tunnel markers, invasion will be analyzed using the vimentin, or SDF1-a markers.
- Radiation toxicity [ Time Frame: Measured at study enrollment, at first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery. ]Toxicity to surrounding breast and skin tissue, defined by ≥ grade 2 fibrosis.
- Surgical wound healing and the overall complication rate. [ Time Frame: Measured at the first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery. ]Percentage of patients experiencing wound infection that requires wound to be opened and/or packed.
- Local recurrence rates [ Time Frame: Disease status will be evaluated at routine patient follow-up appointments, including yearly mammography. Will be reported at year 3. ]Ipsilateral breast recurrence rate.
- Ability of imaging to predict patient response to radiotherapy. [ Time Frame: Pre-treatment imaging to be done after study enrollment (baseline) and 14-20 days after the last dose of neoadjuvant radiation has been delivered. ]Correlation between complete clinical response on imaging and pathological complete response.
- Ability of imaging markers to predict response to radiotherapy [ Time Frame: Pre-treatment imaging to be done after study enrollment (baseline measurements) and 14-20 days after the last dose of neoadjuvant radiation has been delivered. ]Ability of FDG uptake, choline levels, perfusion, and ADC obtained from post-radiotherapy imaging to predict tissue response to high dose radiotherapy.
- Ability to predict pathological response to treatment based on tumour genetics [ Time Frame: Tissue samples for analysis will be taken 14-20 days after completion of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy and will be compared with tissue taken prior to the start of neoadjuvant radiation. ]Ability to predict pathological response to treatment based on microarray analysis of tumor gene expression.
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): NCT03978663
|Contact: Muriel Brackstone, MD PhD||519-685-8500 ext firstname.lastname@example.org|
|Contact: Kalan S Lynn||519-646-6100 ext email@example.com|
|London Regional Cancer Program||Recruiting|
|London, Ontario, Canada|
|Contact: Muriel Brackstone, MD, PhD 519-685-8712 Muriel.Brackstone@lhsc.on.ca|
|Principal Investigator:||Muriel Brackstone, MD PhD||London Health Sciences Centre/Lawson Health Research Institute|
|Study Chair:||Michael Lock, MD||London Health Sciences Centre/London Regional Cancer Program|
|Study Chair:||Brian Yaremko, MD||London Health Sciences Centre/London Regional Cancer Program|