Biomarkers Investigation of Neoadjuvant Chemotherapy for Breast Cancer

NCT ID: NCT03242551

Last Updated: 2017-11-14

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

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-08

Study Completion Date

2022-12-31

Brief Summary

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The BINC-B trial is a diagnostic and interventional study in which various function imaging methods as Magnetic Resonance Imaging (PWI, DWI and DCE-MRI) and will be compared with common imaging methods (mammography and/or ultrasound) to investigate if an early response to a combined neoadjuvant chemotherapy in operable or potentially operable breast cancer. For breast cancer patients with positive HER-2, additional Herceptin could improve the response further. In this study the efficacy of combined neoadjuvant therapy with or without Herceptin should be evaluated and the role in predicting the tumor response with different imaging should be estimated.

Detailed Description

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Firstly, the investigators aim to show that the results of functional imaging including dynamic enhanced, diffuse weighted, and perfusion MR imaging biomarkers as well the ultrasonic outcome could be used to predict the response to the neoadjuvant chemotherapy for operable and potentially operable breast cancer (luminal B, HER-2 positive and triple negative).

Secondly, the investigators will study the role of peripheral blood biomarker including circulating tumor DNA (ctDNA), circulating endothelial cells (CECs) and subsets, myeloid-derived suppressor cells (MDSCs), and lymph cell subsets and their combinations could predict the response of the tumor measured with imaging.

Thirdly, the investigators will establish a mode with these multiple imaging and serum biomarker panel as well as their changes during the treatment course establish to predict the response to neoadjuvant chemotherapy.

Conditions

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Breast Neoplasms

Study Design

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Intervention Model

SEQUENTIAL

epirubicin, paclitaxol, cyclophosphamide, trastuzumab
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Neoadjuvant chemotherapy

Epirubicin 100mg/m2 and cyclophosphamine 600mg/m2 for four cycles followed by paclitaxol 175mg/m2 for four cycles with (for patients with positive HER-2) or without Trastuzumab (loading dose of 6 mg/kg followed by 4 mg/kg every 2 weeks for four cycles), each cycle is 14 days.

Group Type EXPERIMENTAL

Chemotherapy

Intervention Type DRUG

"AC" followed by "T" Chemotherapy with or without trastuzumab, i.e. Epirubicin 100mg/m2 and cyclophosphamine 600mg/m2 for four cycles followed by paclitaxol 175mg/m2 for four cycles with (for patients with positive HER-2) or without Trastuzumab (loading dose of 6 mg/kg followed by 4 mg/kg every 2 weeks for four cycles), each cycle is 14 days.

Interventions

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Chemotherapy

"AC" followed by "T" Chemotherapy with or without trastuzumab, i.e. Epirubicin 100mg/m2 and cyclophosphamine 600mg/m2 for four cycles followed by paclitaxol 175mg/m2 for four cycles with (for patients with positive HER-2) or without Trastuzumab (loading dose of 6 mg/kg followed by 4 mg/kg every 2 weeks for four cycles), each cycle is 14 days.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age ≥18 years and ≤70 years
* Female
* Operable or potentially operable primary breast cancer (≥ cT2, N0 or N+, M0);
* Confirmed by core biopsy
* Histological confirmed unilateral, solitaire breast cancer
* Baseline LVEF ≥55% (measured by echocardiography) according to institution specific norm
* Informed consent for clinical trial including analysis of predictive imaging tests and biomarkers
* Clinically or by imaging (mammogram, MRI or US) assessed breast cancer ≥2 cm with bi-dimensional measurable lesion independent of nodal status
* Negative pregnancy test (urine or serum) within 7 days prior to registration if patient is premenopausal with intact reproductive organs and if patient is less than one year after menopause
* ECOG Performance status 0-2
* Adequate organ function for cytotoxic chemotherapy
* Adequate renal function including Serum creatinine ≤ ULN, Measured or calculated creatinine clearance \> 60 ml per min
* Absolute neutrophil count ≤ 1500/µL, platelet count ≥ 100,000/µL
* Bilirubin ≤ ULN; ALT or AST ≤ 1.5 x ULN, and alkaline phosphatase ≤2.5 x ULN
* Patients must be available and compliant for treatment and follow-up

Exclusion Criteria

* Evidence of distant metastases by clinical or imaging diagnosis
* Multifocal primary tumor, defined as histologically confirmed tumor-manifestations within different quadrants; distance ≥ 4 cm
* Pre-existing motor or sensory neuropathy of a severity ≥ grade 2 NCI criteria
* Previous breast cancer
* Prior malignancy with a disease-free survival of \< 5 year
* Prior malignancy which has not been curatively treated
* Inflammatory breast cancer
* Prior systemic therapy for cancer
* Patients with immunosuppressive therapy
* Pregnant or lactating women
* Women of childbearing potential not using highly effective birth control
* Patients with known hypersensitivity reactions to the compounds or incorporated substances of trastuzumab or its constituents (for HER2+ tumors)
* Invasive malignancy which could affect compliance with the protocol or interpretation of results
* Other serious illness or medical condition including: Known or suspected congestive heart failure (\>NYHA I) and/or coronary heart disease, Angina pectoris requiring antianginal medication; Previous history of myocardial infarction, Evidence of transmural infarction on ECG, Un- or poorly controlled arterial hypertension (i.e. BP \>150/100 mmHg under treatment with two antihypertensive drugs), Rhythm abnormalities requiring permanent treatment; Clinically significant valvular heart disease, Patients with dyspnea at rest due to malignant or other disease or who require supportive oxygen therapy, Active serious uncontrolled infections, Poorly controlled diabetes, History of hypertensive crisis or hypertensive encephalopathy; History of TIA or CVA
* Neutrophil count of \< 1500, platelet count of \< 100,000/µL, Haemoglobin \< 10 g/dL
* Inadequate bone marrow, hepatic and renal functions as evidenced by the following: Serum total bilirubin \> ULN, ALT or AST \> 1.5 x ULN, Alkaline phosphatase \> 2.5 x ULN, serum creatinine \> ULN
* Concurrent treatment with any other anti-cancer therapy
* No informed consent for analysis of predictive imaging tests and biomarkers
* Contraindications against MRI: Cardiac pacemakers, other forms of medical or biostimulation implants, ferromagnetic foreign bodies or metallic implants (e.g. surgical protheses, aneurysm clips), implanted insulin pumps, valvular implants, allergy to contrast agent, renal insufficiency, claustrophobia
* Active peptic ulcer, incomplete wound healing or unhealed bone fracture
* Disease significantly affecting gastrointestinal function, e.g. malabsorption syndrome, resection of the stomach or small bowel, ulcerative colitis, abdominal fistula, intra-abdominal abscess within 6 months of enrolment or gastrointestinal perforation
* Concurrent treatment with other experimental drugs; participation in another clinical trial with any investigational drug within 30 days prior to study entry
* Chronic daily treatment with corticosteroids (dose of \> 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids)
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Shenzhen People's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Wenyong Tan

Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wenyong Tan, Dr.

Role: PRINCIPAL_INVESTIGATOR

Shenzhen People Hospital

Locations

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Department of Oncology

Shenzhen, Guangdong, China

Site Status NOT_YET_RECRUITING

Shenzhen People Hospital

Shenzhen, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Wenyong Tan, Dr

Role: CONTACT

Phone: 008618924672707

Email: [email protected]

Facility Contacts

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Wenyong Tan, Dr

Role: primary

Ming Yang, Ms.

Role: backup

Wenyong Tan, Dr

Role: primary

References

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Marinovich ML, Sardanelli F, Ciatto S, Mamounas E, Brennan M, Macaskill P, Irwig L, von Minckwitz G, Houssami N. Early prediction of pathologic response to neoadjuvant therapy in breast cancer: systematic review of the accuracy of MRI. Breast. 2012 Oct;21(5):669-77. doi: 10.1016/j.breast.2012.07.006. Epub 2012 Aug 3.

Reference Type BACKGROUND
PMID: 22863284 (View on PubMed)

Prevos R, Smidt ML, Tjan-Heijnen VC, van Goethem M, Beets-Tan RG, Wildberger JE, Lobbes MB. Pre-treatment differences and early response monitoring of neoadjuvant chemotherapy in breast cancer patients using magnetic resonance imaging: a systematic review. Eur Radiol. 2012 Dec;22(12):2607-16. doi: 10.1007/s00330-012-2653-5. Epub 2012 Sep 16.

Reference Type BACKGROUND
PMID: 22983282 (View on PubMed)

Braman NM, Etesami M, Prasanna P, Dubchuk C, Gilmore H, Tiwari P, Plecha D, Madabhushi A. Erratum to: Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI. Breast Cancer Res. 2017 Jul 10;19(1):80. doi: 10.1186/s13058-017-0862-1. No abstract available.

Reference Type BACKGROUND
PMID: 28693537 (View on PubMed)

Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. Epub 2013 Apr 7.

Reference Type BACKGROUND
PMID: 23563269 (View on PubMed)

Morganella S, Alexandrov LB, Glodzik D, Zou X, Davies H, Staaf J, Sieuwerts AM, Brinkman AB, Martin S, Ramakrishna M, Butler A, Kim HY, Borg A, Sotiriou C, Futreal PA, Campbell PJ, Span PN, Van Laere S, Lakhani SR, Eyfjord JE, Thompson AM, Stunnenberg HG, van de Vijver MJ, Martens JW, Borresen-Dale AL, Richardson AL, Kong G, Thomas G, Sale J, Rada C, Stratton MR, Birney E, Nik-Zainal S. The topography of mutational processes in breast cancer genomes. Nat Commun. 2016 May 2;7:11383. doi: 10.1038/ncomms11383.

Reference Type BACKGROUND
PMID: 27136393 (View on PubMed)

Other Identifiers

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Shenzhen BC-001

Identifier Type: -

Identifier Source: org_study_id