Genomic-Guided Radiation Therapy for Breast Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Disqualifiers: Pregnancy, Breastfeeding, Metastatic cancer, others
No Placebo Group
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of the study is to determine the feasibility of genomically guided radiation therapy (RT) in people with triple negative (HER2 negative, hormone receptor negative) breast cancer undergoing breast conservation therapy.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment Genomically Guided Radiation Therapy for Breast Cancer?
Research suggests that using genomic information to guide radiation therapy can potentially improve treatment by tailoring it to individual genetic profiles, which may enhance tumor control and reduce side effects. Advances in understanding genetic variations have already been integrated into clinical practice for other cancers, indicating a promising future for personalized radiation therapy in breast cancer.
12345Is Genomic-Guided Radiation Therapy safe for humans?
Research shows that genetic factors can influence how people react to radiation therapy, with some experiencing side effects like skin reactions. However, these side effects are generally related to individual genetic differences, and understanding these can help predict and manage them.
36789How is Genomically Guided Radiation Therapy different from other breast cancer treatments?
Genomically Guided Radiation Therapy is unique because it uses genetic information to tailor radiation treatment specifically to the patient's tumor, potentially improving effectiveness and reducing unnecessary exposure compared to standard radiation therapy, which does not typically use genomic data for personalization.
510111213Eligibility Criteria
This trial is for adults over 18 with triple negative breast cancer who've had a lumpectomy and axillary evaluation. They must not be pregnant or breastfeeding, have recovered from recent surgeries, and agree to use effective contraception. Participants need a life expectancy over 16 weeks and a performance status score of at least 70.Inclusion Criteria
I have had multiple treatments for my condition.
My breast cancer is not driven by hormones.
My breast cancer is confirmed as Triple Negative by a biopsy.
+9 more
Exclusion Criteria
I am not pregnant or breastfeeding.
My breast cancer has spread to other parts of my body.
I am not allergic to any of the drugs or their components used in this study.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive genomically guided radiation therapy or standard radiation therapy based on their Radiosensitivity Index score
6-8 weeks
Weekly visits for radiation therapy
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments of progression-free survival and quality of life
Up to 5 years
Regular follow-up visits
Participant Groups
The study tests genomically guided radiation therapy in patients with triple negative breast cancer following breast conservation surgery. It aims to assess the feasibility of tailoring radiation treatment based on genetic markers.
2Treatment groups
Experimental Treatment
Active Control
Group I: Radiosensitivity Index optimizedExperimental Treatment1 Intervention
Participants will be assigned to optimized arm based on their RSI score. Participants will receive whole breast radiation therapy with or without regional lymph node irradiation as appropriate with or without a boost to the lumpectomy cavity.
Group II: Radiosensitivity Index not optimizedActive Control1 Intervention
Participants will receive standard of care whole breast radiation therapy with or without regional lymph node irradiation as appropriate with a boost to the lumpectomy cavity.
Genomically Guided Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Radiation Therapy for:
- Breast cancer
- Ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
- Prostate cancer
- Pancreatic cancer
- Brain tumors
- Spinal cord tumors
🇺🇸 Approved in United States as Radiation Therapy for:
- Breast cancer
- Ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
- Prostate cancer
- Pancreatic cancer
- Brain tumors
- Spinal cord tumors
- Non-Hodgkin’s lymphoma
🇨🇦 Approved in Canada as Radiation Therapy for:
- Breast cancer
- Ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
- Prostate cancer
- Pancreatic cancer
- Brain tumors
- Spinal cord tumors
🇯🇵 Approved in Japan as Radiation Therapy for:
- Breast cancer
- Ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
- Prostate cancer
- Pancreatic cancer
- Brain tumors
- Spinal cord tumors
🇨🇳 Approved in China as Radiation Therapy for:
- Breast cancer
- Ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
- Prostate cancer
- Pancreatic cancer
- Brain tumors
- Spinal cord tumors
🇨🇭 Approved in Switzerland as Radiation Therapy for:
- Breast cancer
- Ovarian cancer
- Fallopian tube cancer
- Peritoneal cancer
- Prostate cancer
- Pancreatic cancer
- Brain tumors
- Spinal cord tumors
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
Morton Plant Hospital - Baycare Health SystemClearwater, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
References
Applying Precision Oncology Principles in Radiation Oncology. [2020]Radiation therapy is a critical component in the curative management of many solid tumor types, and advances in radiation delivery techniques during the past decade have led to improved disease control and quality of life for patients. During the same period, remarkable advances have also been made in understanding the genomic landscape of tumors; however, treatment decisions in radiation oncology continue to depend primarily on clinical and histopathologic characteristics rather than on the genetic features of the tumor or the patient. With the development of novel genomic techniques and their increasing use in clinical practice, radiation oncology is uniquely positioned to leverage these advances to identify novel biomarkers that could inform radiation dose, field, and the use of concurrent systemic agents. Here, we summarize efforts to use genomic techniques to guide radiation decisions, and we highlight some of the current opportunities and challenges that exist in attempting to apply precision oncology principles in radiation oncology.
The Role of Genomic Techniques in Predicting Response to Radiation Therapy. [2018]The understanding of the relationship between genetic variation and an individual patient's response to radiation therapy (RT) has gained significant ground over the past several years. Genetic markers have been identified that could ultimately serve as the foundation for predictive models in clinical practice, and that hold the potential to revolutionize the delivery of precision medicine in oncology. Single nucleotide polymorphisms, single genes, and/or gene signatures could ultimately serve as the basis for patient stratification in prospective clinical trials. Currently, molecular markers relevant to breast, lung, and head and neck cancers have been integrated into clinical practice and serve as predictive tools to guide systemic therapy. In the future, the use of predictive models based on genomic determinants may become standard practice in radiation oncology, offering the potential to further personalize the delivery of RT and optimize the therapeutic ratio.
Genetics and genomics of radiotherapy toxicity: towards prediction. [2022]Radiotherapy is involved in many curative treatments of cancer; millions of survivors live with the consequences of treatment, and toxicity in a minority limits the radiation doses that can be safely prescribed to the majority. Radiogenomics is the whole genome application of radiogenetics, which studies the influence of genetic variation on radiation response. Work in the area focuses on uncovering the underlying genetic causes of individual variation in sensitivity to radiation, which is important for effective, safe treatment. In this review, we highlight recent advances in radiotherapy and discuss results from four genome-wide studies of radiotoxicity.
Radiogenomics in the Era of Advanced Radiotherapy. [2020]Most radiogenomics studies investigate how genetic variation can help to explain the differences in early and late radiotherapy toxicity between individuals. The field of radiogenomics in photon beam therapy has grown rapidly in recent years, carving out a unique translational discipline, which has progressed from candidate gene studies to larger scale genome-wide association studies, meta-analyses and now prospective validation studies. Genotyping is increasingly sophisticated and affordable, and whole-genome sequencing may soon become readily available as a diagnostic tool in the clinic. The ultimate aim of radiogenomics research is to tailor treatment to the individual with a test based on a combination of treatment, clinical and genetic factors. This personalisation would allow the greatest tumour control while minimising acute and long-term toxicity. Here we discuss the evolution of the field of radiogenomics with reference to the most recent developments and challenges.
Tumor control probability predictions for genetic radiotherapy. [2019]Genetic radiotherapy, the combination of gene therapy and radiation therapy, for cancer treatment is evolving from laboratory studies to clinical trials. Genetic radiotherapy involves the viral infection of cells that change the sensitivity of transduced cells to radiation. Because there is no patient outcome data for genetic radiotherapy, prospective models are needed to determine the expected benefit of this new modality. Such a prospective model has been developed in this work.
The influence of BRCA1/BRCA2 mutations on toxicity related to chemotherapy and radiotherapy in early breast cancer patients. [2014]The presence of BRCA gene mutation and low expressions of BRCA proteins are associated with a greater sensitivity of tumor cells to ionizing radiation and to cytostatics damaging the DNA of the cells. The purpose of this study was to estimate the rate of adverse events in BRCA1/2-associated breast cancer patients receiving anthracycline-based chemotherapy compared to patients without mutation. The authors also compared radiotherapy toxicity in these 2 groups.
Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy. [2021]Normal-tissue adverse effects following radiotherapy are common and significantly affect quality of life. These effects cannot be accounted for by dosimetric, treatment, or demographic factors alone, and evidence suggests that common genetic variants are associated with radiotherapy adverse effects. The field of radiogenomics has evolved to identify such genetic risk factors. Radiogenomics has two goals: (i) to develop an assay to predict which patients with cancer are most likely to develop radiation injuries resulting from radiotherapy, and (ii) to obtain information about the molecular pathways responsible for radiation-induced normal-tissue toxicities. This review summarizes the history of the field and current research.
Breast Radiation Therapy-Related Treatment Outcomes in Patients With or Without Germline Mutations on Multigene Panel Testing. [2023]Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing.
Association Between Polymorphisms in DNA Damage Repair Genes and Radiation Therapy-Induced Early Adverse Skin Reactions in a Breast Cancer Population: A Polygenic Risk Score Approach. [2020]Genetic variations in DNA damage repair (DDR) genes may influence radiation therapy (RT)-induced acute normal tissue toxicity in patients with breast cancer. Identifying an individual or multiple single-nucleotide polymorphisms (SNPs) associated with RT-induced early adverse skin reactions (EASR) is critical for precision medicine in radiation oncology.
DEGRO guidelines for the radiotherapy of non-malignant disorders : part III: hyperproliferative disorders. [2022]Radiation therapy (RT) is an established and effective treatment modality in the management of a large variety of hyperproliferative disorders and benign neoplasms. Objective of this article is to summarize the updated DEGRO consensus S2e guideline recommendations.
Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer. [2021]Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy.
Pathologic Response to Neoadjuvant Sequential Chemoradiation Therapy in Locally Advanced Breast Cancer: Preliminary, Translational Results from the French Neo-APBI-01 Trial. [2023]Radiation therapy (RT), a novel approach to boost the anticancer immune response, has been progressively evaluated in the neoadjuvant setting in breast cancer (BC).
[Genetic bases of the radiosensitivity of breast cancer]. [2009]Local-regional radiation therapy is one of the major therapeutic means in the management of breast cancer. Three questions however arise from the important advances achieved in this domain in the past years. The first question concerns the possibilities to identify and overcome the radioresistance of a subset of tumours. The second question is how to recognize women likely to benefit from adjuvant radiation therapy, and therefore to diminish treatment indications in other groups. Finally, the third question is how to identify subjects at high risk for long term injury following breast irradiation, in order to adapt techniques and indications in such populations. The major advances of breast cancer molecular genetics in the past years should provide clinicians with tools to answer these important questions. In this paper, we review the molecular germline (BRCA1, BRCA2, ATM, ...) and somatic (p53, tyrosine kinase receptors, as well as actors of cell cycle, signal transduction, apoptosis, DNA repair ...) main bases of breast cancer radiosensitivity. Recent methods of exploration of the genetic background of both the host and the tumours (gene and protein expression profiles) are also reviewed as major tools of breast cancer management in the next few years.