Study of Tumor RNA Disruption Assay™ (RDA) (RnaDx)

Study of Tumor RNA Disruption Assay™ (RDA) and Its Association With a Response to Neoadjuvant Chemotherapy in Breast Cancer - A Prospective Mixed-Methods Study

The purpose of this study is to find out if the pathological complete response (pCR) to chemotherapy given before surgery (neoadjuvant chemotherapy) could be predicted by the evaluation of the RNA (ribonucleic acids) disruption pattern (RNA Disruption Assay or RDA score) obtained from a biopsy of the tumor 7 - 14 days after the first, second and third cycles of chemotherapy treatment. If we can determine the optimal time during neoadjuvant chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast cancer management.

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasms
• Intervention / Treatment: Other: Tumor RNA Disruption Assay™ (RDA)

Detailed Description

When administering neoadjuvant chemotherapy, the current practice of monitoring response to treatment is by measuring the size of the breast tumor after each cycle of chemotherapy. The drawback to this method is, it will take several weeks before we can actually measure a significant change in size; and the initial response to chemotherapy is often evident as a softening of the tumor without an apparent decrease of the tumor size. Finding a reliable way to identify early response to chemotherapy would be helpful to enable matching of chemotherapy to an individual's need.

In a previous trial of breast cancer treated with neoadjuvant chemotherapy, researchers have identified that the pCR to a full treatment of chemotherapy could be predicted by the change in RNA pattern obtained from a biopsy of the tumor half way through the chemotherapy course. [Parissenti et al. 2010] The purpose of this study is to determine if we can predict the pCR to neoadjuvant chemotherapy by examining the pattern of RNA disruption (RNA Disruption Assay or RDA score) from breast biopsy tissue obtained 7 to 14 days after the first, second and third cycle of chemotherapy. If we can determine the optimal time during neoadjuvant chemotherapy to measure the RDA score for the prediction of pCR, we can optimize breast cancer management. For example, if RDA score can identify non-responders earlier, we can switch to other chemotherapy agents and reduce the exposure to the unnecessary side-effects of ineffective treatment.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences Juravinski Cancer Centre
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St Michael's Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Odette Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female,18 years or older;
• Able to read and write in English:
• With palpable cancer > 2cm (T2, T3) on clinical examination or clinical diagnosis of locally advanced breast cancer (LABC) (T3 or T4; or N2 or N3, according to TNM cancer staging including inflammatory breast cancer);
• Must have histological proof of breast cancer (invasive ductal or infiltrating lobular);
• Scheduled to receive neoadjuvant chemotherapy as part of their treatment plan;
• Agree to have FNAB after the first, second and third cycle of chemotherapy, and if the chemotherapy regimen is changed, an additional FNAB after the first cycle of the new chemotherapy.

Exclusion Criteria:

• Subjects who have had surgery, neoadjuvant chemotherapy or radiotherapy for the current breast cancer;
• Subjects who are pregnant or breast feeding;
• Subjects with Stage IV breast cancer;
• Psychiatric or addictive disorders that may limit the ability to give informed consent or complete the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tumor RNA Disruption Assay™ (RDA); Tumor RNA Disruption Assay™ (RDA) to generate RDA score from fine needle aspiration biopsy samples of breast cancer obtained 7-14 days after the first, second and third cycles of neoadjuvant chemotherapy; and, if there is a change of chemotherapy regimen, after the first cycle of the new chemotherapy.	Other: Tumor RNA Disruption Assay™ (RDA); Tumor RNA Disruption Assay™ (RDA) to generate RDA score from fine needle aspiration biopsy samples of breast cancer obtained 7-14 days after the first, second and third cycles of neoadjuvant chemotherapy; and, if there is a change of chemotherapy regimen, after the first cycle of the new chemotherapy.; Other Names: Biomarker

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between RDA score and pathological complete response (pCR)	The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and the pCR to neoadjuvant chemotherapy will be evaluated. pCR is defined as no evidence of invasive carcinoma in the breast and lymph nodes (ypT0/Tis ypN0/N0itc) on histology at the time of surgery (lumpectomy or mastectomy).	An expected average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The prognostic ability of RDA score	The capacity of RDA score to predict pCR to neoadjuvant chemotherapy will be assessed by exploring for a cut point on the RDA score to differentiate subjects with a high likelihood of achieving pCR versus those who are less likely to achieve pCR.	An expected average of 6 months
The association between RDA score and clinical response (cR)	The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and clinical response to neoadjuvant chemotherapy treatment will be evaluated.	An expected average of 6 months
Patients' perception of fine needle aspiration biopsy (FNAB) and of breast cancer care	We shall seek to understand the experiences of patients with the FNAB procedure and with the cancer care they received while participating in the study by conducting qualitative interviews of study subjects.	An expected average of 12 months
The cost-effectiveness of using RDA score	The cost-effectiveness of using RDA score to guide neoadjuvant chemotherapy will be evaluated by measuring the cost-effectiveness of monitoring pCR to neoadjuvant chemotherapy through the RDA score and in modifying the neoadjuvant chemotherapy regimen for non-pCR patients accordingly.	An expected average of 6 months
The association between RDA score and Disease-Free Survival (DFS)	The association between tumor RDA score measured 7-14 days after the first, second and third cycles of chemotherapy and DFS will be evaluated. DFS will be measured as the time from patient's enrollment to the event of cancer metastasis or recurrence, or death, whatever comes first.	An expected average of 5 years

Collaborators and Investigators

• Sponsor: University of Toronto
• Collaborators: University Health Network, Toronto
• Investigators: Principal Investigator: Murray Krahn, MD,MSc,FRCPC, Director of THETA Collaborative, the F. Norman Hughes Chair in Pharmacoeconomics and Social and Administrative Pharmacy Division Head in the Faculty of Pharmacy, Professor at the University of Toronto

Publications and helpful links

General Publications

• Parissenti AM, Chapman JA, Kahn HJ, Guo B, Han L, O'Brien P, Clemons MP, Jong R, Dent R, Fitzgerald B, Pritchard KI, Shepherd LE, Trudeau ME. Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2010 Jan;119(2):347-56. doi: 10.1007/s10549-009-0531-x.
• Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M, Lightfoot S, Menzel W, Granzow M, Ragg T. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006 Jan 31;7:3. doi: 10.1186/1471-2199-7-3.
• Guidance for Industry- Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval (May 2012). US DHHS FDA CDER; Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM305501.pdf

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: September 2, 2014
• First Submitted That Met QC Criteria: September 10, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Actual): October 26, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Neoadjuvant chemotherapy; Breast cancers; RNA Disruption Assay™ (RDA) score; Pathological Complete Response (pCR); Fine Needle Aspiration Biopsy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 495462