RNA Disruption Assay for Breast Cancer

(BREVITY Trial)

Recruiting at6 trial locations

Overseen by Foluso Ademuyiwa, M.D.

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Rna Diagnostics Inc.

Must not be taking: Experimental drugs

Disqualifiers: Stage IV breast cancer, Pregnancy, others

Stay on Your Current Meds

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new method called RNA Disruption Assay to see if it can help doctors determine early on if breast cancer patients' tumors are responding to chemotherapy. By analyzing the tumor's RNA, the test aims to guide treatment decisions and improve patient outcomes.

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 is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the RNA Disruption Assay treatment for breast cancer?

Research shows that the RNA Disruption Assay (RDA) can predict which breast cancer patients will respond well to chemotherapy. Patients with high RNA disruption in their tumors had better survival rates and were more likely to have a complete response to treatment. ^{1 2 3 4 5}

How does the RNA Disruption Assay treatment differ from other breast cancer treatments?

The RNA Disruption Assay (RDA) is unique because it measures the level of RNA disruption in tumor cells during chemotherapy, which can predict the effectiveness of the treatment and guide adjustments. This approach allows for early identification of non-responders to chemotherapy, potentially improving survival by switching to alternative treatments sooner. ^{1 2 5 6 7}

Research Team

Thierry Petit

Principal Investigator

Institut de Cancérologie, Strasbourg, France

Foluso Ademuyiwa, M.D.

Principal Investigator

Washington University School of Medicine, St Louis, USA

Joke Tio, MD

Principal Investigator

Munster, Germany

Maureen E Trudeau, MD

Principal Investigator

Sunnybrook Health Sciences Center, Toronto, Canada

Daniele Generali, MD

Principal Investigator

SST di Cremona Multidisciplinare di Patologia Mammaria, Italy

Tomasz Jankowski, MD

Principal Investigator

NZOZ Neuromed, Lublin, Poland

Eva Ciruelos, MD

Principal Investigator

Madrid, Spain

Eligibility Criteria

This trial is for women over 18 with stage I-III breast cancer, aiming to have surgery after chemotherapy. They must be able to consent and agree to two core needle biopsies during treatment. Excluded are those with stage IV cancer, concurrent serious conditions, prior treatments for current cancer, or in another drug trial.

Inclusion Criteria

I am a woman aged 18 or older.

I am scheduled for initial treatment with chemotherapy and possibly other drugs before surgery.

I have stage I, II, or III breast cancer and aim for surgery after initial treatment.

Exclusion Criteria

I have had treatment for my current breast cancer.

Concurrent medical, psychiatric or addictive disorders that may limit the ability to give informed consent or complete the trial

I am not in another trial for my breast cancer that involves experimental drugs.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive standard of care neoadjuvant chemotherapy treatments including taxanes, anthracyclines, or other targeted drugs and drug combinations

Approximately 8-12 weeks

Bi-weekly or weekly visits depending on drug schedule

Biopsy Collection and RDA Analysis

Two core needle biopsy specimens are taken at each biopsy collection time point for RDA analysis during neoadjuvant chemotherapy

35 +/- 4 days after initiation of chemotherapy and potentially 2-3 weeks after therapy change

2 visits for biopsy collection

Surgery

Surgery is performed to assess pathological complete response (pCR) and residual cancer burden (RCB)

At completion of neoadjuvant therapy

Follow-up

Participants are monitored for disease-free survival and other outcomes

60 months

Regular follow-up visits

Treatment Details

Interventions

• RNA Disruption Assay (RDA) (RNA Disruption Assay)

Trial Overview The study tests the RNA Disruption Assay (RDA) as a tool to assess tumor response from biopsy samples taken during neoadjuvant chemotherapy. It aims to validate RDA's effectiveness in predicting treatment outcomes before surgical excision.

Participant Groups

Group I: Single Interventional Study Arm Experimental Treatment 1 Intervention

There will be 2 biopsy collection time points with 2 core needle biopsy specimens taken at each biopsy collection time point for RDA analysis during neoadjuvant chemotherapy.

Who Is Running the Clinical Trial?

Rna Diagnostics Inc.

Lead Sponsor

Trials

1

Recruited

800+

Findings from Research

The RNA disruption assay (RDA) developed in this study identified more chemotherapy non-responders than traditional clinical assessments, suggesting it is a more effective biomarker for evaluating treatment response in breast cancer patients.

Patients with high RNA disruption (Zone 3) had significantly better disease-free survival (DFS) rates, even comparable to those achieving a pathologic complete response (pCR), indicating that RDA could guide chemotherapy decisions more effectively than pCR alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy. Parissenti, AM., Guo, B., Pritzker, LB., et al.[2016]

A new RNA disruption assay (RDA) can effectively stratify breast cancer patients into responders and non-responders to treatment based on RNA quality changes observed as early as 14 days into therapy, potentially guiding treatment decisions.

In a clinical trial involving 85 patients, the RDA successfully identified 38 patients likely to achieve a pathological complete response (pCR), indicating its potential as a reliable intermediate endpoint for assessing treatment efficacy in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy. Pritzker, K., Pritzker, L., Generali, D., et al.[2018]

DDX1 RNA overexpression is identified as a strong independent prognostic marker for early recurrence in breast cancer, with a hazard ratio of 4.31, indicating a significantly increased risk of relapse despite standard treatment.

Elevated levels of DDX1 protein in the cytoplasm also correlate with early recurrence, with a hazard ratio of 1.90, suggesting that both DDX1 RNA and protein levels could be valuable biomarkers for predicting poor outcomes in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer. Germain, DR., Graham, K., Glubrecht, DD., et al.[2015]

In the CAN-NCIC-MA22 trial involving 50 women with locally advanced or inflammatory breast cancer, low mid-treatment RNA integrity number (RIN) was linked to higher chemotherapy doses and a better pathologic complete response (pCR), indicating its potential as a biomarker for treatment response.

Post-treatment analysis showed that low tumor cellularity was associated with a better pCR, and this was particularly evident in patients with high baseline progesterone receptor levels, suggesting that both RIN and tumor cellularity could be important indicators of chemotherapy effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients. Parissenti, AM., Chapman, JA., Kahn, HJ., et al.[2018]

RNA disruption, which involves the degradation of ribosomal RNA during chemotherapy, is linked to better treatment outcomes in breast cancer, including complete pathological response and improved disease-free survival.

This study shows that RNA disruption occurs in various cell types in response to different stressors, such as chemotherapy and oxidative stress, and is associated with significant indicators of cell death, suggesting its potential as a biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells. Butler, P., Pascheto, I., Lizzi, M., et al.[2023]

Higher levels of RARalpha mRNA in breast carcinoma samples correlate with estrogen receptor (ER) positivity, suggesting that RARalpha may play a role in the growth inhibition of ER-positive breast cancers.

RARalpha mRNA levels could potentially serve as a marker to predict how responsive patients might be to retinoic acid therapy, especially since they are low or absent in ER-negative samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of the retinoic Acid nuclear receptors (rars) and retinoid x-receptor (rxr) genes in estrogen-receptor positive and negative breast-cancer. Shao, Z., Sheikh, M., Chen, J., et al.[2019]

The gene RAI3 is frequently overexpressed in estrogen receptor-negative breast cancers, with increased levels found in 19 out of 25 primary tumors and 6 out of 11 cancer cell lines, suggesting its role in breast cancer development.

Suppressing RAI3 using siRNA in breast cancer cell lines led to reduced cell growth, indicating that targeting RAI3 could be a promising new strategy for treating breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of RAI3 as a therapeutic target for breast cancer. Nagahata, T., Sato, T., Tomura, A., et al.[2007]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy. [2016]

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

RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer. [2015]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients. [2018]

5. England pubmed.ncbi.nlm.nih.gov

RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells. [2023]

6. Greece pubmed.ncbi.nlm.nih.gov

Expression of the retinoic Acid nuclear receptors (rars) and retinoid x-receptor (rxr) genes in estrogen-receptor positive and negative breast-cancer. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Identification of RAI3 as a therapeutic target for breast cancer. [2007]