Genomic-Guided Radiation Therapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Robin Dowell

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Disqualifiers: Pregnancy, Breastfeeding, Metastatic cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

86 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{3 6 7 8 9}

How 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. ^{5 10 11 12 13}

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.

Research Team

Kamran Ahmed, M.D.

Principal Investigator

Moffitt Cancer Center

Eligibility 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.

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.

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

Treatment Details

Interventions

• Genomically Guided Radiation Therapy

Trial Overview 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.

Participant Groups

Group I: Radiosensitivity Index optimized Experimental Treatment 1 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 optimized Active Control 1 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

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Findings from Research

Recent advancements in radiation therapy have significantly improved disease control and quality of life for patients with solid tumors, but treatment decisions still largely rely on clinical and histopathologic factors rather than genetic information.

There is a growing opportunity to integrate genomic techniques into radiation oncology, which could lead to the identification of biomarkers that help tailor radiation treatment plans, including dosage and the use of systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applying Precision Oncology Principles in Radiation Oncology. Kamran, SC., Mouw, KW.[2020]

Recent advancements have identified genetic markers that can predict how individual patients respond to radiation therapy, paving the way for more personalized treatment in oncology.

Currently, molecular markers for cancers like breast, lung, and head and neck are already being used in clinical practice to guide therapy, and future predictive models based on genetic information may enhance the effectiveness of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Genomic Techniques in Predicting Response to Radiation Therapy. Williams, NL., Dan, T., Zaorsky, NG., et al.[2018]

Radiogenomics aims to understand how genetic differences affect individual responses to radiation therapy, which is crucial for personalizing cancer treatment and minimizing toxicity.

Recent genome-wide studies have provided insights into the genetic factors that contribute to variations in radiotoxicity, helping to improve the safety and effectiveness of radiotherapy for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetics and genomics of radiotherapy toxicity: towards prediction. West, CM., Barnett, GC.[2022]

Radiogenomics is advancing rapidly, moving from candidate gene studies to larger genome-wide association studies and prospective validation, aiming to personalize radiotherapy based on genetic factors to improve treatment outcomes.

The goal of this research is to optimize cancer treatment by combining genetic, clinical, and treatment data, which could enhance tumor control while reducing the risk of both acute and long-term side effects from radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiogenomics in the Era of Advanced Radiotherapy. Brothwell, MRS., West, CM., Dunning, AM., et al.[2020]

A new model for genetic radiotherapy predicts a potential increase in tumor control probability (TCP) by up to 15% compared to traditional radiotherapy, using reasonable values for transduction fraction and enhancement factor.

The model suggests that with improved techniques, TCP could theoretically increase by nearly 70%, allowing for significant dose reductions in radiation therapy while maintaining tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor control probability predictions for genetic radiotherapy. Keall, PJ., Lammering, G., Lin, PS., et al.[2019]

In a study of 270 early-stage breast cancer patients, those with BRCA1/2 mutations experienced a higher rate of neutropenia (32%) after the first cycle of anthracycline-based chemotherapy compared to non-carriers (10%).

Non-carriers reported more severe nausea and vomiting (13% vs. 7%), while BRCA mutation carriers showed increased radiation toxicity, particularly after mastectomy and neoadjuvant chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of BRCA1/BRCA2 mutations on toxicity related to chemotherapy and radiotherapy in early breast cancer patients. Huszno, J., Budryk, M., Kołosza, Z., et al.[2014]

Radiogenomics aims to identify genetic variants that predict which cancer patients are at higher risk for adverse effects from radiotherapy, potentially improving treatment personalization.

A predictive assay based on single-nucleotide polymorphisms could help estimate the risk of radiation injuries, allowing for tailored therapies that enhance patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy. Kerns, SL., Ostrer, H., Rosenstein, BS.[2021]

In a study of 286 women with breast cancer, those with pathogenic variant (PV) mutations, including BRCA1/2 and non-BRCA1/2 mutations, showed similar oncologic outcomes and toxicity rates after receiving radiation therapy compared to patients without mutations.

The findings support the use of adjuvant radiation therapy as a standard treatment for breast cancer, regardless of the presence of germline mutations, as there were no significant differences in overall survival, locoregional recurrence, or disease-specific death among the groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast Radiation Therapy-Related Treatment Outcomes in Patients With or Without Germline Mutations on Multigene Panel Testing. Chapman, BV., Liu, D., Shen, Y., et al.[2023]

In a study of 416 breast cancer patients, 27.6% experienced early adverse skin reactions (EASR) after radiation therapy, with significant associations found between EASR and specific genetic variations in five DNA damage repair genes: ATM, CHEK1, ERCC2, RAD51C, and TGFB1.

Nine specific single-nucleotide polymorphisms (SNPs) within these genes were identified as potential predictors of EASR, and a polygenic risk score model indicated that patients with higher genetic risk scores were significantly more likely to develop EASR, highlighting the importance of genetic factors in personalizing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lee, E., Eum, SY., Slifer, SH., et al.[2020]

Radiation therapy (RT) is an effective treatment for various conditions, including Morbus Dupuytren, keloids, and desmoid tumors, with evidence supporting its use across multiple disorders.

The updated DEGRO guidelines classify the strength of evidence for RT's efficacy as ranging from level 2c to 4, indicating it can be a primary treatment or a valuable adjunct to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DEGRO guidelines for the radiotherapy of non-malignant disorders : part III: hyperproliferative disorders. Seegenschmiedt, MH., Micke, O., Niewald, M., et al.[2022]

The Adjuvant Radiotherapy Intensification Classifier (ARTIC), developed from a study of 748 patients, effectively predicts locoregional recurrence (LRR) risk and the benefit of radiotherapy (RT) after breast-conserving surgery, showing a significant hazard ratio of 3.4 for LRR in patients treated with RT.

Patients with low ARTIC scores experienced a substantial reduction in LRR risk with RT, while those with high scores showed less benefit, indicating that ARTIC can help tailor RT strategies for better outcomes in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer. Sjöström, M., Chang, SL., Fishbane, N., et al.[2021]

In a study of 42 patients with locally advanced breast cancer, the neoadjuvant chemoradiation therapy (NACRT) showed a pathologic complete response (pCR) rate of 38%, slightly higher than the 33% pCR rate observed with standard neoadjuvant chemotherapy (NACT).

Baseline factors such as hemoglobin levels of ≥13 g/dL and a body mass index of <26 were strongly associated with better responses to NACRT, indicating that these parameters could help personalize treatment for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathologic Response to Neoadjuvant Sequential Chemoradiation Therapy in Locally Advanced Breast Cancer: Preliminary, Translational Results from the French Neo-APBI-01 Trial. To, NH., Gabelle-Flandin, I., Luong, TMH., et al.[2023]

Recent advances in breast cancer molecular genetics can help identify which tumors are resistant to radiation therapy, potentially leading to more effective treatment strategies.

Understanding the genetic background of both patients and tumors may allow clinicians to better predict who will benefit from radiation therapy and who is at risk for long-term side effects, improving overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Genetic bases of the radiosensitivity of breast cancer]. Delaloge, S., Marsiglia, H.[2009]

References

1. United States pubmed.ncbi.nlm.nih.gov

Applying Precision Oncology Principles in Radiation Oncology. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

The Role of Genomic Techniques in Predicting Response to Radiation Therapy. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Genetics and genomics of radiotherapy toxicity: towards prediction. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Radiogenomics in the Era of Advanced Radiotherapy. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Tumor control probability predictions for genetic radiotherapy. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The influence of BRCA1/BRCA2 mutations on toxicity related to chemotherapy and radiotherapy in early breast cancer patients. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Breast Radiation Therapy-Related Treatment Outcomes in Patients With or Without Germline Mutations on Multigene Panel Testing. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

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]

10. Germany pubmed.ncbi.nlm.nih.gov

DEGRO guidelines for the radiotherapy of non-malignant disorders : part III: hyperproliferative disorders. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Pathologic Response to Neoadjuvant Sequential Chemoradiation Therapy in Locally Advanced Breast Cancer: Preliminary, Translational Results from the French Neo-APBI-01 Trial. [2023]

13. France pubmed.ncbi.nlm.nih.gov

[Genetic bases of the radiosensitivity of breast cancer]. [2009]