Clinical trial NCT02239315: Study of Tumor RNA Disruption Assay™ (RDA)
Official title: Study of Tumor RNA Disruption Assay™ (RDA) and Its Association With a Response to Neoadjuvant Chemotherapy in Breast Cancer - A Prospective Mixed-Methods Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Breast Neoplasms
Keywords: Breast cancers
Neoadjuvant chemotherapy
RNA Disruption Assay™ (RDA) score
Pathological Complete Response (pCR)
Fine Needle Aspiration Biopsy
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2014-09-12
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The association between RDA score and pathological complete response (pCR)
timeFrame: An expected average of 6 months
Secondary outcomes:
measure: The prognostic ability of RDA score
timeFrame: An expected average of 6 months
measure: The association between RDA score and clinical response (cR)
timeFrame: An expected average of 6 months
measure: Patients' perception of fine needle aspiration biopsy (FNAB) and of breast cancer care
timeFrame: An expected average of 12 months
measure: The cost-effectiveness of using RDA score
timeFrame: An expected average of 6 months
measure: The association between RDA score and Disease-Free Survival (DFS)
timeFrame: An expected average of 5 years
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Juravinski Cancer Centre
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
Study officials:
affiliation: 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
name: Murray Krahn, MD,MSc,FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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