Monitoring Response to NAC and Prediction of pCR in Breast Cancer Patients Using Optical Imaging

NCT ID: NCT04767659

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-27

Study Completion Date

2025-08-30

Brief Summary

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Neoadjuvant chemotherapy (NAC) is the first line treatment for locally advanced breast cancer (BC). Besides making breast conserving surgery feasible, its main aim is to achieve a pathological complete response (pCR). Previous studies demonstrated that a pCR correlated with a higher disease-free survival. Tumor response may vary among different BC subtypes and only 30% of BC respond completely to NAC. Treating chemo-resistant disease with NAC may cause patient harm due to drug toxicity and surgery delay.

It is therefore very important to promptly identify those women who will not benefit from NAC.

Mammography and ultrasound proved ineffective in monitoring changes in lesion size due to therapy-induced fibrosis. MRI is the most accurate imaging technique for assessing early clinical response by measuring tumor size, however its accuracy is lower post NAC. This necessitates the need for a new technique able to non invasively assess the effectiveness of NAC. Optical techniques are sensitive to the biological changes that occur within the tumor after NAC administration. These changes occur prior to tumor size reduction.

Optically estimated total hemoglobin concentration correlates with the histological analysis of vasculature as well as with tumor-associated angiogenesis which can affect tumor changes during NAC. Other promising biomarkers related to tissue composition (water, lipid, collagen content) and structure (scattering) may also be evaluated by optical techniques.

The aim of the study is to monitor the effectiveness of NAC in BC patients with a near infrared spectroscopic imaging platform which allows to non-invasively detect changes in vascularization and size of BC and to characterize the presence of temporal changes in regional concentrations of relevant biomarkers (oxy- and deoxyhemoglobin, water, lipid and collagen concentration, scattering) within tissue during NAC.

This optical imaging technique will provide a non-invasive, safe and relatively inexpensive tool to monitor patients' response to NAC and to predict their outcome.

Detailed Description

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In this study, an accurate, reliable, non-invasive modality with good patient tolerance will be tested to predict response to NAC in order to tailor the medical and surgical treatment.

The aim of this project is to monitor the effectiveness of NAC in BC patients with a new near infrared spectroscopic imaging platform which allows to non-invasively detect changes in size, vascularization and blood oxygenation in tumors and to characterize the presence of temporal changes in regional concentrations of relevant biomarkers like oxy- and deoxyhemoglobin, water, lipid and collagen and scattering in the tissue during NAC. This optical imaging tool will allow a non-invasive, safe and relatively inexpensive monitoring of NAC and prediction of patients' outcome.

A single-site, national, non-comparative, non-randomized study will be conducted at the San Raffaele Hospital in Milan in collaboration with the Politecnico di Milano. The medical device is a prototype developed by Politecnico di Milano.

Twenty adult women with a recent diagnosis of breast cancer and candidate for NAC, who fulfil the inclusion criteria and agree to voluntary participate in the study under informed consent, will be enrolled.

Besides assessing the response to neoadjuvant chemotherapy using conventional imaging evaluation (x-ray mammography and breast ultrasound prior to commencement/baseline, half way through and on completion of NAC; contrast-enhanced MRI prior to commencement/baseline and on completion of NAC), the patients enrolled will be evaluated with optical imaging at the following six selected time points (prior to commencement of NAC/baseline, 2-5 days post-NAC, 6-8 days post-NAC, 2 weeks post-NAC, half-way through and on completion of NAC).

A preliminary phase will be performed on the first 5 patients out of the 20 patients enrolled, in order to evaluate the potential artefacts related to a recent breast biopsy and to the positioning of a clip. In this preliminary phase, 2 additional optical evaluations will be carried out, one prior to the breast biopsy and one after the positioning of the clip.

Patients are enrolled in the study for the entire duration of NAC. No follow-up is required and patients will be followed according to the regular clinical standard of care. Moreover, the outcome of the optical investigation does not affect the treatment and management of the women enrolled in the study.

The duration of enrolment of the study is expected to be approximately 12 months. The study will end when the last patient enrolled will complete her chemotherapy treatment.

Conditions

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Breast Cancer Female Chemotherapy Effect

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Women candidate for clinical trial

Twenty adult women with a recent diagnosis of breast cancer, candidate for NAC, besides assessing the response to neoadjuvant chemotherapy using standard imaging evaluation, will undergo optical imaging at six selected time points from prior to commencement of NAC/baseline to the completion of NAC treatment (prior to surgery).

Group Type EXPERIMENTAL

MAMMOT2

Intervention Type DEVICE

Breast cancer patients candidate for neoadjuvant chemotherapy will be evaluated with optical imaging prior to commencement of NAC/baseline, 2-5 days post-NAC, 6-8 days post-NAC, 2 weeks post-NAC, half-way through and on completion of NAC. 2 additional optical evaluations will be carried out on the first 5 patients enrolled, one before breast biopsy and one after the positioning of the metallic clip, in order to evaluate the potential artefacts related to these procedures.

Interventions

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MAMMOT2

Breast cancer patients candidate for neoadjuvant chemotherapy will be evaluated with optical imaging prior to commencement of NAC/baseline, 2-5 days post-NAC, 6-8 days post-NAC, 2 weeks post-NAC, half-way through and on completion of NAC. 2 additional optical evaluations will be carried out on the first 5 patients enrolled, one before breast biopsy and one after the positioning of the metallic clip, in order to evaluate the potential artefacts related to these procedures.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Women above 18 years of age
* Women with a recent diagnosis of breast cancer candidate for neoadjuvant chemotherapy
* Women willing to give informed consent

Exclusion Criteria

* Subject is pregnant or breastfeeding
* Subject is unable or unwilling to give informed consent
* Previous surgery of the same breast
* Presence of distant metastasis
* Breast implants
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Politecnico di Milano

OTHER

Sponsor Role collaborator

IRCCS San Raffaele

OTHER

Sponsor Role lead

Responsible Party

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Pietro Panizza

Head of Breast Imaging Unit, MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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PANIZZA

Role: PRINCIPAL_INVESTIGATOR

IRCCS San Raffaele

Locations

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Ospedale San Raffaele

Milan, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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PIETRO PANIZZA, PI

Role: CONTACT

02-26436310

CAROLINA SANTANGELO

Role: CONTACT

Facility Contacts

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PIETRO PANIZZA

Role: primary

References

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Wabnitz H, Taubert DR, Mazurenka M, Steinkellner O, Jelzow A, Macdonald R, Milej D, Sawosz P, Kacprzak M, Liebert A, Cooper R, Hebden J, Pifferi A, Farina A, Bargigia I, Contini D, Caffini M, Zucchelli L, Spinelli L, Cubeddu R, Torricelli A. Performance assessment of time-domain optical brain imagers, part 1: basic instrumental performance protocol. J Biomed Opt. 2014 Aug;19(8):086010. doi: 10.1117/1.JBO.19.8.086010.

Reference Type BACKGROUND
PMID: 25121479 (View on PubMed)

Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012 Nov 17;380(9855):1778-86. doi: 10.1016/S0140-6736(12)61611-0. Epub 2012 Oct 30.

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Reference Type BACKGROUND
PMID: 26778289 (View on PubMed)

Durduran T, Choe R, Baker WB, Yodh AG. Diffuse Optics for Tissue Monitoring and Tomography. Rep Prog Phys. 2010 Jul;73(7):076701. doi: 10.1088/0034-4885/73/7/076701.

Reference Type BACKGROUND
PMID: 26120204 (View on PubMed)

Leff DR, Warren OJ, Enfield LC, Gibson A, Athanasiou T, Patten DK, Hebden J, Yang GZ, Darzi A. Diffuse optical imaging of the healthy and diseased breast: a systematic review. Breast Cancer Res Treat. 2008 Mar;108(1):9-22. doi: 10.1007/s10549-007-9582-z. Epub 2007 Apr 28.

Reference Type BACKGROUND
PMID: 17468951 (View on PubMed)

Taroni P, Pifferi A, Salvagnini E, Spinelli L, Torricelli A, Cubeddu R. Seven-wavelength time-resolved optical mammography extending beyond 1000 nm for breast collagen quantification. Opt Express. 2009 Aug 31;17(18):15932-46. doi: 10.1364/OE.17.015932.

Reference Type BACKGROUND
PMID: 19724592 (View on PubMed)

Ferocino E, Martinenghi E, Dalla Mora A, Pifferi A, Cubeddu R, Taroni P. High throughput detection chain for time domain optical mammography. Biomed Opt Express. 2018 Jan 23;9(2):755-770. doi: 10.1364/BOE.9.000755. eCollection 2018 Feb 1.

Reference Type BACKGROUND
PMID: 29552410 (View on PubMed)

Quarto G, Spinelli L, Pifferi A, Torricelli A, Cubeddu R, Abbate F, Balestreri N, Menna S, Cassano E, Taroni P. Estimate of tissue composition in malignant and benign breast lesions by time-domain optical mammography. Biomed Opt Express. 2014 Sep 18;5(10):3684-98. doi: 10.1364/BOE.5.003684. eCollection 2014 Oct 1.

Reference Type BACKGROUND
PMID: 25360382 (View on PubMed)

Taroni P, Quarto G, Pifferi A, Ieva F, Paganoni AM, Abbate F, Balestreri N, Menna S, Cassano E, Cubeddu R. Optical identification of subjects at high risk for developing breast cancer. J Biomed Opt. 2013 Jun;18(6):060507. doi: 10.1117/1.JBO.18.6.060507.

Reference Type BACKGROUND
PMID: 23804215 (View on PubMed)

Taroni P, Paganoni AM, Ieva F, Pifferi A, Quarto G, Abbate F, Cassano E, Cubeddu R. Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study. Sci Rep. 2017 Jan 16;7:40683. doi: 10.1038/srep40683.

Reference Type BACKGROUND
PMID: 28091596 (View on PubMed)

Pearlman PC, Adams A, Elias SG, Mali WP, Viergever MA, Pluim JP. Mono- and multimodal registration of optical breast images. J Biomed Opt. 2012 Aug;17(8):080901-1. doi: 10.1117/1.JBO.17.8.080901.

Reference Type BACKGROUND
PMID: 23224161 (View on PubMed)

Tavakoli B, Zhu Q. Two-step reconstruction method using global optimization and conjugate gradient for ultrasound-guided diffuse optical tomography. J Biomed Opt. 2013 Jan;18(1):16006. doi: 10.1117/1.JBO.18.1.016006.

Reference Type BACKGROUND
PMID: 23296038 (View on PubMed)

Other Identifiers

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NADOPTIC

Identifier Type: -

Identifier Source: org_study_id

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