RNA Disruption Assay for Breast Cancer

(BREVITY Trial)

Recruiting at 7 trial locations

Overseen By Sanaa Noubir, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Rna Diagnostics Inc.

Must not be taking: Experimental drugs

Disqualifiers: Stage IV breast cancer, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 2

801 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a tool called the RNA Disruption Assay (RDA) to measure how breast cancer tumors respond to chemotherapy. Researchers take small samples from the tumor at specific times during treatment to analyze changes. Women diagnosed with stage I, II, or III breast cancer, who are about to start chemotherapy and have a tumor size of at least 1 cm, might be suitable candidates. Participants must agree to undergo two needle biopsies during their chemotherapy sessions. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance future breast cancer treatments.

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 prior data suggests that the RNA Disruption Assay is safe for use in breast cancer patients?

Research has shown that the RNA Disruption Assay (RDA) is being studied to assess breast cancer tumors' response to chemotherapy. This method does not involve testing a new drug but evaluates the effectiveness of existing treatments. Studies have found that applying RDA to tumor samples can help predict a patient's response to chemotherapy.

RDA focuses on analyzing tumor samples without introducing new drugs or chemicals into the body. It involves taking small tissue samples, known as biopsies, at specific times. This method is generally well-tolerated, as it uses procedures similar to those already employed in cancer care.

In summary, RDA measures how tumors respond to treatment and is not a treatment itself. It is considered safe because it involves procedures familiar to patients undergoing cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the RNA Disruption Assay (RDA) for breast cancer because it offers a new way to assess how well neoadjuvant chemotherapy is working. Unlike traditional methods that rely on imaging or waiting until surgery to evaluate treatment effectiveness, RDA can provide insights earlier by analyzing biopsy samples at different points during treatment. This means doctors might be able to adjust treatment plans more quickly, potentially improving outcomes for patients.

What evidence suggests that the RNA Disruption Assay is effective for assessing tumour response in breast cancer?

Research has shown that the RNA Disruption Assay (RDA) might help predict breast cancer's response to chemotherapy. Studies have found that higher RNA disruption values during treatment often link to better outcomes, such as complete tumor disappearance after therapy. In this trial, participants will undergo RDA analysis during neoadjuvant chemotherapy. Patients with RNA disruption levels above 1.1 during treatment tended to respond more favorably. This suggests that RDA could be useful in assessing chemotherapy's effectiveness for a patient's tumor. Overall, the test seems promising as a tool to measure treatment success early on. ^{1 4 6 7 8}

Who Is on the 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

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

Joke Tio, MD

Principal Investigator

Munster, Germany

Tomasz Jankowski, MD

Principal Investigator

NZOZ Neuromed, Lublin, Poland

Eva Ciruelos, MD

Principal Investigator

Madrid, Spain

Are You a Good Fit for This Trial?

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 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.

I am willing to undergo 2 needle biopsies during my 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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• RNA Disruption Assay (RDA)

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03524430

RNA Disruption Assay (RDA)-Breast Cancer Response ... The current study aims to provide validation results of RNA Disruption Assay (RDA) as a tumour response assessment tool that uses tumour core biopsies.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12337404/

High mid-treatment tumour RNA disruption in patients with ... Tumour RDI values were higher mid- and post-treatment than pre-treatment (p < 0.0001). Patients with tumour RDI values > 1.1 exhibited higher ...

3. nature.com nature.com/articles/s41598-023-28635-8

RNA disruption is a widespread phenomenon associated ... Extensive tumour RNA disruption during chemotherapy was associated with a post-treatment pathological complete response and improved disease- ...

4. withpower.com withpower.com/trial/phase-breast-neoplasms-3-2018-95bf5

RNA Disruption Assay for Breast Cancer (BREVITY 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 ...

5. rnadiagnostics.com rnadiagnostics.com/wp-content/uploads/2024/02/Low-RNA-disruption-during-neoadjuvant-chemotherapy-predicts-pathologic-complete-response-absence-in-patients-with-breast-cancer.pdf

Low-RNA-disruption-during-neoadjuvant-chemotherapy- ... These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly ...

6. aacrjournals.org aacrjournals.org/cancerres/article/82/4_Supplement/OT2-03-01/680297/Abstract-OT2-03-01-RNA-disruption-assay-RDA-Breast

Abstract OT2-03-01: RNA disruption assay (RDA) - Breast ... Abstract OT2-03-01: RNA disruption assay (RDA) - Breast cancer response evaluation for individualized therapy (brevity/brevity-02) Available.

7. nature.com nature.com/articles/s41598-020-65579-9

The RNA disruption assay is superior to conventional drug ... Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy. Breast Cancer Res. Treat. 153, 135–144 (2015). Article CAS ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02190227

RNA Disruption Assay (RDA) Response Prediction in ... The purpose of this study is to determine the optimal time to use the Tumor RNA Disruption Assay (RDA) as a predictor of pathological complete response (pCR) in ...