Neoadjuvant Treatment of Breast Cancer

Sponsor

National Institute of Oncology, Hungary (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05131893

Collaborator

(none)

300

Enrollment

Location

117

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Observational investigation of participants who are given neoadjuvant treatment for invasive breast cancer. The scope of the study is to collect information on standardized treatment results, to explore the causes of dose modification and its effect on efficacy, to explore potential prognostic factors, and to explore the long-term side effects of different treatment modalities.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Tamoxifen Drug: Goserelin Drug: Letrozole 2.5Mg Tab Drug: Epirubicin Drug: cyclophosphamide Drug: Docetaxel Drug: paclitaxel Drug: trastuzumab Drug: pertuzumab Drug: Capecitabine

Detailed Description

The purpose of the study is based on the uniform application of international guidelines in Hungarian conditions. The standardized circumstances may lead to optimization of neoadjuvant therapy, it may facilitate subsequent data analysis, provide a basis for prospective clinical questions, and demonstrate improvement in pathologic complete remission (pCR) and overall survival (OS) compared to historical control. It may make possible to collect real-life data on each therapeutic option: efficacy, side effects, dose reduction, dose intensity, long-term consequences. The main scope is to collect prospective data to explore prognostic and predictive factors. The auxiliary aim is the assessment and comparison of quality of life during specific treatments and their side effects.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Neoadjuvant Treatment of Breast Cancer - a Prospective Observational Study, PANnon ONCology (PANONC) Group Non-commercial Clinical Trial

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Dec 1, 2031

Arms and Interventions

Arm	Intervention/Treatment
LuminalA tamoxifen (+ LHRH analogue for premenopausal participant) non-steroidal aromatase inhibitor (+ LHRH analogue for premenopausal participant) Non-steroidal aromatase inhibitor in non-resectable tumor (+ LHRH analogue in premenopausal participant) + CDK4 / 6 inhibitor	Drug: Tamoxifen endocrine therapy Drug: Goserelin endocrine therapy Drug: Letrozole 2.5Mg Tab endocrine therapy Other Names: letrozole
LuminalB (Her2 negative) 12 times weekly paclitaxel (80 mg / m˄2) followed by 4 times every 3 weeks epirubicin (E) (90-100 mg / m˄2) + cyclophosphamide (C) (600) (preferred) 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 12x weekly paclitaxel (80mg / m˄2) 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 12x weekly paclitaxel (80mg / m˄2) TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)	Drug: Tamoxifen endocrine therapy Drug: Goserelin endocrine therapy Drug: Letrozole 2.5Mg Tab endocrine therapy Other Names: letrozole Drug: Epirubicin chemotherapy Drug: cyclophosphamide chemotherapy Drug: Docetaxel chemotherapy Drug: paclitaxel chemotherapy Drug: trastuzumab biological treatment
Her2 positive 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab Docetaxel (75 mg / m˄2) + carboplatin (AUC6) + trastuzumab +/- pertuzumab 6 times every 3 weeks c) E (90-100mg / m˄2) + C (600mg / m˄2) 4x every 2 weeks, then 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly)	Drug: Tamoxifen endocrine therapy Drug: Goserelin endocrine therapy Drug: Letrozole 2.5Mg Tab endocrine therapy Other Names: letrozole Drug: Epirubicin chemotherapy Drug: cyclophosphamide chemotherapy Drug: Docetaxel chemotherapy Drug: paclitaxel chemotherapy Drug: trastuzumab biological treatment Drug: pertuzumab biological treatment
Triple-negative breast cancer Paclitaxel (80 mg / m˄2) +/- carboplatin (AUC2) 12 times weekly, then E (90-100 mg / m˄2) + C (600 mg / m˄2) 4 times three weekly (preferred) 4x every 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 4x docetaxel (90-100mg / m˄2) or 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 ) 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 4 times every 2 weeks paclitaxel (175 mg / m˄2) or 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)	Drug: Epirubicin chemotherapy Drug: cyclophosphamide chemotherapy Drug: Docetaxel chemotherapy Drug: paclitaxel chemotherapy Drug: Capecitabine chemotherapy

Outcome Measures

Primary Outcome Measures

pathological complete remission rate [3 year, maximum]
no invasive tumor in breast and axilla

Secondary Outcome Measures

invasive disease-free survival [10 years]
from the beginning of neoadjuvant therapy to the first appearance of invasive tumor or death
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [4 years]
Global health status, functional and symptom scales survey using the EORTC QLQ-C30 questionnaire before cycle 1, before cycle 4, after the last neoadjuvant chemotherapy, and before surgery, 1 year after chemotherapy
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ BR45) [4 years]
Breast cancer-specific functional scales and symptom scales survey using the EORTC QLQ BR45 questionnaire before cycle 1, before cycle 4, after the last neoadjuvant chemotherapy, and before surgery, 1 year after chemotherapy
evaluation of side effects [10 years]
to collect information all potential complaints and adverse event during and after treatment

Other Outcome Measures

dose density assessment [3 year, maximum]
actual dose / planned dose
investigate the potential prognostic effect of neutrophil/lymphocyte ratio [10 years]
study of the role of neutrophil/lymphocyte ratio (NLR) at baseline, before the 3. cycle, and before surgery. NLR is measured from the qualitative blood count as the absolute neutrophil count divided by the absolute lymphocyte count
investigate the potential prognostic effect of monocyte/lymphocyte ratio [10 years]
monocyte/lymphocyte ratio (MLR) at baseline, before the 3. cycle, and before surgery. MLR is measured from the qualitative blood count as the absolute monocyte count divided by the absolute lymphocyte count
investigate potential prognostic factors, CRP [10 years]
C-reactive protein serum level befor start of chemotherapy
investigate potential prognostic factors [10 years]
circulating free-DNA at baseline, before 3. cycle, before surgery

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant over 18 years of age .
Histologically confirmed (core biopsy) invasive breast tumor.
Tumor extent for the indication:

regression must be achieved for radical surgical removal or
regression is required for breast-conserving surgery or
if hormone receptor (HR)-positive and Her2-: stage IIB (cT2N1 or cT3NO) - IIIC,
if HR-negative: stage IIA (cT2N0 or cT0-1N1) - IIIC Note: In the case of a locally advanced, irresectable case, if the possibility of radical surgery later is a realistic goal, the participant may be included in the study.

Appropriate general condition: ECOG 0-1
Proper organ function

Neutrophil count ≥ 1.5 G / l, platelet count ≥ 100 G / l, hemoglobin ≥ 10 g / dl
Alanine aminotransferase (ALT) / aspartate aminotransferase (AST) is less than 1.5 times the upper limit of the normal range
bilirubin less than 1.5 times the upper limit of the normal range (except Gilbert's disease, where less than 3 times)
creatinine less than 1.5 times the upper limit of the normal range or estimated glomerular filtration rate (eGFR) higher than 60 ml / min

Exclusion Criteria:

Proven or suspected distant metastasis.
No staging studies have been performed: at least chest x-ray, abdominal ultrasound. It is preferred to perform CT from the chest, abdomen, pelvic regions and bone isotope, or PET / CT if possible in case of lymph node involvement.
Known significant heart disease: major arrhythmia or significant conduction defect (grade 2 or more), infarction or unstable angina within 6 months, cardiac collapse without appropriate therapy, long QT syndrome, heart failure (≥New York Heart Association/NYHA II)
Other severe acute or chronic conditions (organic or psychiatric illness, laboratory abnormality) that, in the opinion of the treating physician, result in an unacceptable increase in the risk of chemotherapy and are contraindicated in routine clinical practice.
Pregnancy or if the participant does not agree to use an appropriate non-hormonal method of contraception.