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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to radiation therapy for individuals with triple negative breast cancer, a type that does not respond to common hormone treatments. The study aims to determine if a genomic profile can enhance the effectiveness of radiation therapy. Participants will receive either genomically guided radiation therapy, tailored to their genetic makeup, or standard radiation treatment. This trial suits individuals who have already undergone a lumpectomy for triple negative breast cancer. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to advancements in personalized cancer 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 prior data suggests that genomically guided radiation therapy is safe for breast cancer patients?

Research has shown that using genomics to guide radiation therapy offers a promising way to treat breast cancer. This approach customizes radiation treatment based on the tumor's genetic details, aiming to enhance effectiveness and reduce harm.

Previous studies found that patients with certain genetic traits did not experience increased sensitivity to radiation, indicating that the treatment is generally well-tolerated. By focusing on genetic information, the radiation dose can be adjusted, potentially reducing side effects.

As this study remains in the early stages, safety is still under assessment. Current findings suggest some evidence of safety, but further research is needed to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about genomically guided radiation therapy for breast cancer because it personalizes treatment based on a patient’s unique genetic makeup. Unlike standard radiation therapy, which is generally uniform for all patients, this approach uses a Radiosensitivity Index (RSI) to determine how sensitive a patient's cancer cells are to radiation. This allows for a more tailored treatment plan that could potentially enhance effectiveness and reduce side effects. By optimizing radiation doses specifically for each individual, this method aims to improve outcomes and offer a more targeted approach to fighting breast cancer.

What evidence suggests that genomically guided radiation therapy could be effective for breast cancer?

Research has shown that genomically guided radiation therapy could be promising for treating breast cancer, particularly triple-negative breast cancer. This trial will compare two approaches: one arm will use a Radiosensitivity Index-optimized method, adjusting the radiation dose based on the tumor's genetic details to potentially enhance treatment effectiveness. The other arm will use standard radiation therapy. The genomic-adjusted radiation dose (GARD) customizes the radiation treatment, making it more precise for each patient. Early results suggest this approach might reduce the chance of cancer recurrence by targeting cancer cells more accurately. This method aims to improve outcomes by focusing on the cancer's unique features. ^{1 2 3 6 7}

Who Is on the Research Team?

Kamran Ahmed, M.D.

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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.

My surgery showed cancer cells at the edge of the tissue removed.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8361058/

Genomically Guided Breast Radiation Therapy: A Review of ... A critical review of the current literature on the use of genomics in breast radiation therapy was undertaken by a group of breast radiation oncologists.

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05528133

NCT05528133 | Genomically Guided Radiation Therapy in ... The purpose of the study is to determine the feasibility of genomically guided radiation therapy (RT) in people with triple negative (HER2 negative, hormone ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2839036

Adjuvant Radiation and Endocrine Therapy in Early-Stage ... Meaning These findings suggest that adjuvant RT or ET can significantly reduce the risk of LRR among patients with early-stage breast cancer and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0960977623005143

Individualising radiation therapy decisions in breast cancer ... The genomic-adjusted radiation dose (GARD) is a non-breast cancer specific, tumour genomic biomarker introduced to personalise the radiation prescription dose.

5. moffitt.org moffitt.org/for-healthcare-professionals/clinical-perspectives/clinical-perspectives-story-archive/new-clinical-trial-aims-to-genomically-personalize-radiation-therapy-for-breast-cancer/

New Clinical Trial Aims to Genomically Personalize ... Moffitt researchers are testing the feasibility of genomically guided radiation therapy to improve outcomes in triple-negative breast cancer ...

6. mdpi.com mdpi.com/2072-6694/15/22/5314

Moving the Needle Forward in Genomically-Guided ... Clinically, patients with either germline heterozygous BRCA1 or BRCA2 mutations have not been shown to experience increased radiation sensitivity compared to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12384496/

Narrative Review of the Use of Genomic-Adjusted Radiation ... This review explains how the genomic-adjusted radiation dose (GARD) can be used to personalize radiation therapy based on a tumor's genetic ...