Predicting BReast cAncer Response to neoadjuVant Therapy by ctDNA Assessment

Официальное название

Investigate the Prognostic and Predictive Value of Circulating Tumor DNA (ctDNA) During Neoadjuvant Chemotherapy for Breast Cancer.

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Determine the detection rate and change of ctDNA in blood samples of cancer patients before, during, and after neoadjuvant treatment. [Срок оценки: 12 months following up.]
• To investigate the relationship between ctDNA expression and MRI imaging with pCR response in neo-adjuvant therapy. [Срок оценки: 12 months following up.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Вьетнам · 2 центра

• Medical Genetics Institute — Ho Chi Minh City
• University Medical Center HCMC — Ho Chi Minh City

Индонезия · 1 центр

• MRCCC Siloam Hospitals Semanggi — Jakarta

Публикации

• 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 b PMID 30528802
• 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 N PMID 29327055
• 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-pacl PMID 26869049
• 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, PMID 29501363
• 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-nega PMID 31095287
• 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 r PMID 35182721
• 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, v PMID 24529560
• 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. PMID 30396301

Идентификаторы

NCT: NCT06087120 · GS_ZNAB

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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