Predicting BReast cAncer Response to neoadjuVant Therapy by ctDNA Assessment

NCT ID: NCT06087120

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 125 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-09-16
• Study Completion Date: 2025-12-31

Brief Summary

This is a prospective and observational study, aiming to determine the detection rate and change of CtDNA in blood samples of cancer patients before, during and after neoadjuvant treatment.

• Determine the rate of ctDNA positivity at the time before treatment,
• Determine the rate of ctDNA positivity at the time during treatment,
• Determine the rate of ctDNA positivity at the time after neoadjuvant therapy, whether there is a change in ctDNA expression of the study population during treatment.

And aiming to investigate the relationship between ctDNA expression and MRI imaging with pCR response in neo-adjuvant therapy:

• Correlation between ctDNA detection and pCR response. Determine the percentage of Positive Prediction Value - PPV, Negative Prediction Value - NPV of ctDNA,
• Correlation between MRI imaging and pCR response. Determination of PPV, NPV of MRI
• Combination of ctDNA detection and MRI imaging in the prognosis of pCR. Determination of PPV, NPV ratio of ctDNA combined with MRI.

Detailed Description

This is a prospective and observational study recruiting Female participants aged 18 and older, who are diagnosed with stage II-III HER+/Triple Negative Breast cancer and indicated for neoadjuvant chemotherapy at University Medical Center HCMC, had FFPE sample at the time of diagnosis and operation. This study is conducted at the Medical Genetics Institute (MGI), and MRCCC Siloam Hospitals Semanggi (Indonesia) in collaboration with the University Medical Center HCMC.

Eligible neoadjuvant chemotherapy (NAC) / treatment regimen for the study:

• AC-T (Doxorubicin, Cyclophosphamid - Taxane).
• AC-TH (Doxorubicin, Cyclophosphamid - Taxane - Trastuzumab).
• TCH (Docetaxel - Carboplatin - Trastuzumab).
• TCHP (Docetaxel - Carboplatin - Trastuzumab - Pertuzumab).

Patients are allowed to change protocol if required clinically.

The potential and voluntary participants, satisfy all the inclusion/exclusion criteria will be recruited into this study.

At enrollment, each participant will answer to the pre-designed questionnaires of demographic information, medical history.

At routine visits, the participants' clinical information and routine para-clinical results such as breast ultrasound or MRI or CT scan, chest x-ray, mamography, bone or PET-CT scan, CA 15-3 will be collected by Physicians.

Participant in this study will have samples collected the following period of time.

• At enrollment (Pre-NAC, at diagnosis): 10ml of peripheral blood for ctDNA analysis and 6-8 sections of formalin-fixed paraffin-embedded (FFPE) tumor samples collected as biopsy before treatment.
• During NAC, 10ml of peripheral blood will be collected for ctDNA analysis and Ultrasound scan of neck, breast, abdomen and pelvis; chest x-ray, CA15-3; CT Scan of the neck, abdomen and pelvis (if any) will be also collected.
• Post-NAC, 10ml of peripheral blood will be collected for ctDNA analysis and Ultrasound scan of neck, breast, abdomen and pelvis; chest x-ray, CA15-3; CT Scan of the neck, abdomen and pelvis, PET-CT scan (if any) will be also collected to compare to treatment respondence between ctDNA and imaging groups.
• After surgery, 6-8 sections of formalin-fixed paraffin-embedded (FFPE) tumor samples collected.

The study end date of a participant is estimated 1 year since enrollment date.

Conditions

Breast Cancer Female; Stage II Breast Cancer; Stage III Breast Cancer; HER2-positive Breast Cancer; Triple Negative Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Female,18 years old and older,
• Are diagnosed with stage II-III HER2+/Triple Negative breast cancer and indicated for neoadjuvant chemotherapy,
• FFPE sample is available at the time of diagnosis and operation,
• Are voluntary to participate in the study.

Exclusion Criteria

• Recurrent breast cancer,
• Other cancer metastasis to the breast,
• Have been or are being treated for cancer,
• Patients did not agree to participate in the studies.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gene Solutions

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sinh D Nguyen, PHD

Role: PRINCIPAL_INVESTIGATOR

MGI

Trung Q Lam, MD

Role: PRINCIPAL_INVESTIGATOR

University medical center HCMC

Samuel J Haryono, MD

Role: PRINCIPAL_INVESTIGATOR

MRCCC Siloam Hospitals Semanggi

Locations

MRCCC Siloam Hospitals Semanggi

Jakarta, , Indonesia

Site Status: RECRUITING

Medical Genetics Institute

Ho Chi Minh City, , Vietnam

Site Status: RECRUITING

University Medical Center HCMC

Ho Chi Minh City, , Vietnam

Site Status: RECRUITING

Countries

Indonesia; Vietnam

Central Contacts

Lan NL Tu, PHD

Role: CONTACT

lantu@genesolutions.vn

+84888843489

Van T. Phan, MSc

Role: CONTACT

vanphan@genesolutions.vn

+84908145990

Facility Contacts

Samuel J Haryono, MD

Role: primary

samuelharyono@dharmaissurgonc.com

(+62) 021 56967525

Lan NL Tu, PhD

Role: primary

lantu@genesolutions.vn

+84888843489

Trung Q Lam, MD

Role: primary

References

Schneeweiss A, Mobus V, Tesch H, Hanusch C, Denkert C, Lubbe K, Huober J, Klare P, Kummel S, Untch M, Kast K, Jackisch C, Thomalla J, Ingold-Heppner B, Blohmer JU, Rezai M, Frank M, Engels K, Rhiem K, Fasching PA, Nekljudova V, von Minckwitz G, Loibl S. Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. Eur J Cancer. 2019 Jan;106:181-192. doi: 10.1016/j.ejca.2018.10.015. Epub 2018 Dec 5.

Reference Type: BACKGROUND

PMID: 30528802 (View on PubMed)

Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA, Magazzu D, De Fato R, Valagussa P, Tusquets I. Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial: A Randomized Phase 3 Clinical Trial. JAMA Oncol. 2018 Mar 1;4(3):302-308. doi: 10.1001/jamaoncol.2017.4612.

Reference Type: BACKGROUND

PMID: 29327055 (View on PubMed)

Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kummel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG); Arbeitsgemeinschaft Gynakologische Onkologie-Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):345-356. doi: 10.1016/S1470-2045(15)00542-2. Epub 2016 Feb 8.

Reference Type: BACKGROUND

PMID: 26869049 (View on PubMed)

Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. doi: 10.1016/S1470-2045(18)30111-6. Epub 2018 Feb 28.

Reference Type: BACKGROUND

PMID: 29501363 (View on PubMed)

Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, Engels K, Rezai M, Jackisch C, Schmitt WD, von Minckwitz G, Thomalla J, Kummel S, Rautenberg B, Fasching PA, Weber K, Rhiem K, Denkert C, Schneeweiss A. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019 Aug 1;30(8):1279-1288. doi: 10.1093/annonc/mdz158.

Reference Type: BACKGROUND

PMID: 31095287 (View on PubMed)

Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, Anton A, Zambelli S, Bianchini G, Russo S, Ciruelos EM, Greil R, Semiglazov V, Colleoni M, Kelly C, Mariani G, Del Mastro L, Maffeis I, Valagussa P, Viale G. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann Oncol. 2022 May;33(5):534-543. doi: 10.1016/j.annonc.2022.02.004. Epub 2022 Feb 17.

Reference Type: BACKGROUND

PMID: 35182721 (View on PubMed)

Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14.

Reference Type: BACKGROUND

PMID: 24529560 (View on PubMed)

Giannone G, Milani A, Geuna E, Galizia D, Biello F, Montemurro F. What is the best pharmacotherapeutic strategy for HER-2 positive breast cancer? Expert Opin Pharmacother. 2019 Jan;20(1):5-9. doi: 10.1080/14656566.2018.1543406. Epub 2018 Nov 6. No abstract available.

Reference Type: BACKGROUND

PMID: 30396301 (View on PubMed)

Montemurro F, Nuzzolese I, Ponzone R. Neoadjuvant or adjuvant chemotherapy in early breast cancer? Expert Opin Pharmacother. 2020 Jun;21(9):1071-1082. doi: 10.1080/14656566.2020.1746273. Epub 2020 Apr 1.

Reference Type: BACKGROUND

PMID: 32237920 (View on PubMed)

Stoetzer OJ, Fersching DM, Salat C, Steinkohl O, Gabka CJ, Hamann U, Braun M, Feller AM, Heinemann V, Siegele B, Nagel D, Holdenrieder S. Circulating immunogenic cell death biomarkers HMGB1 and RAGE in breast cancer patients during neoadjuvant chemotherapy. Tumour Biol. 2013 Feb;34(1):81-90. doi: 10.1007/s13277-012-0513-1. Epub 2012 Sep 15.

Reference Type: BACKGROUND

PMID: 22983919 (View on PubMed)

Bottini A, Berruti A, Tampellini M, Morrica B, Brunelli A, Gnocchi E, Brizzi MP, Aguggini S, Fara E, Alquati P, Dogliotti L. Influence of neoadjuvant chemotherapy on serum tumor markers CA 15-3, MCA, CEA, TPS and TPA in breast cancer patients with operable disease. Tumour Biol. 1997;18(5):301-10. doi: 10.1159/000218043.

Reference Type: BACKGROUND

PMID: 9276030 (View on PubMed)

Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.

Reference Type: BACKGROUND

PMID: 24553385 (View on PubMed)

Swarup V, Rajeswari MR. Circulating (cell-free) nucleic acids--a promising, non-invasive tool for early detection of several human diseases. FEBS Lett. 2007 Mar 6;581(5):795-9. doi: 10.1016/j.febslet.2007.01.051. Epub 2007 Feb 2.

Reference Type: BACKGROUND

PMID: 17289032 (View on PubMed)

Ortolan E, Appierto V, Silvestri M, Miceli R, Veneroni S, Folli S, Pruneri G, Vingiani A, Belfiore A, Cappelletti V, Vismara M, Dell'Angelo F, De Cecco L, Bianchi GV, de Braud FG, Daidone MG, Di Cosimo S. Blood-based genomics of triple-negative breast cancer progression in patients treated with neoadjuvant chemotherapy. ESMO Open. 2021 Apr;6(2):100086. doi: 10.1016/j.esmoop.2021.100086. Epub 2021 Mar 17.

Reference Type: BACKGROUND

PMID: 33743331 (View on PubMed)

Cavallone L, Aguilar-Mahecha A, Lafleur J, Brousse S, Aldamry M, Roseshter T, Lan C, Alirezaie N, Bareke E, Majewski J, Ferrario C, Hassan S, Discepola F, Seguin C, Mihalcioiu C, Marcus EA, Robidoux A, Roy JA, Pelmus M, Basik M. Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer. Sci Rep. 2020 Sep 7;10(1):14704. doi: 10.1038/s41598-020-71236-y.

Reference Type: BACKGROUND

PMID: 32895401 (View on PubMed)

Cailleux F, Agostinetto E, Lambertini M, Rothe F, Wu HT, Balcioglu M, Kalashnikova E, Vincent D, Viglietti G, Gombos A, Papagiannis A, Veys I, Awada A, Sethi H, Aleshin A, Larsimont D, Sotiriou C, Venet D, Ignatiadis M. Circulating Tumor DNA After Neoadjuvant Chemotherapy in Breast Cancer Is Associated With Disease Relapse. JCO Precis Oncol. 2022 Sep;6:e2200148. doi: 10.1200/PO.22.00148.

Reference Type: BACKGROUND

PMID: 36170624 (View on PubMed)

Magbanua MJM, Li W, Wolf DM, Yau C, Hirst GL, Swigart LB, Newitt DC, Gibbs J, Delson AL, Kalashnikova E, Aleshin A, Zimmermann B, Chien AJ, Tripathy D, Esserman L, Hylton N, van 't Veer L. Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk. NPJ Breast Cancer. 2021 Mar 25;7(1):32. doi: 10.1038/s41523-021-00239-3.

Reference Type: BACKGROUND

PMID: 33767190 (View on PubMed)

Lin PH, Wang MY, Lo C, Tsai LW, Yen TC, Huang TY, Huang WC, Yang K, Chen CK, Fan SC, Kuo SH, Huang CS. Circulating Tumor DNA as a Predictive Marker of Recurrence for Patients With Stage II-III Breast Cancer Treated With Neoadjuvant Therapy. Front Oncol. 2021 Nov 12;11:736769. doi: 10.3389/fonc.2021.736769. eCollection 2021.

Reference Type: BACKGROUND

PMID: 34868925 (View on PubMed)

Magbanua MJM, Swigart LB, Wu HT, Hirst GL, Yau C, Wolf DM, Tin A, Salari R, Shchegrova S, Pawar H, Delson AL, DeMichele A, Liu MC, Chien AJ, Tripathy D, Asare S, Lin CJ, Billings P, Aleshin A, Sethi H, Louie M, Zimmermann B, Esserman LJ, van 't Veer LJ. Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol. 2021 Feb;32(2):229-239. doi: 10.1016/j.annonc.2020.11.007. Epub 2020 Nov 21.

Reference Type: BACKGROUND

PMID: 33232761 (View on PubMed)

Zhou Q, Gampenrieder SP, Frantal S, Rinnerthaler G, Singer CF, Egle D, Pfeiler G, Bartsch R, Wette V, Pichler A, Petru E, Dubsky PC, Bago-Horvath Z, Fesl C, Rudas M, Stahlberg A, Graf R, Weber S, Dandachi N, Filipits M, Gnant M, Balic M, Heitzer E. Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response. Clin Cancer Res. 2022 Feb 15;28(4):697-707. doi: 10.1158/1078-0432.CCR-21-3231.

Reference Type: BACKGROUND

PMID: 34862246 (View on PubMed)

Related Links

http://thuvienphapluat.vn/van-ban/The-thao-Y-te/Quyet-dinh-3128-QD-BYT-2020-tai-lieu-chuyen-mon-Huong-dan-chan-doan-dieu-tri-ung-thu-vu-447853.aspx

Health Mo: Decision No. 3128/QD-BYT on the issuance of GUIDES FOR DIAGNOSIS AND TREATMENT OF BREAST CANCER. 2020.

Other Identifiers

GS_ZNAB

Identifier Type: -

Identifier Source: org_study_id