Neoadjuvant Treatment of Breast Cancer

Not yet recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Tamoxifen; Drug: Goserelin; Drug: Letrozole 2.5Mg Tab; Drug: Epirubicin; Drug: cyclophosphamide; Drug: Capecitabine; Drug: Docetaxel; Drug: paclitaxel; Drug: trastuzumab; Drug: pertuzumab

• Registration Number: NCT05131893
• Lead Sponsor: National Institute of Oncology, Hungary

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.

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 Timeline

• Study First Submitted: 2021-07-30
• Status Verified: 2021-11
• Study First Submitted QC: 2021-11-20
• Last Update Submitted: 2021-11-20
• Study First Posted: 2021-11-23
• Last Update Posted: 2021-11-23
• Study Start: 2022-03
• Primary Completion: 2023-03
• Study Completion: 2031-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Participant over 18 years of age .

2. Histologically confirmed (core biopsy) invasive breast tumor.

3. 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.

4. Appropriate general condition: ECOG 0-1

5. 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

1. Proven or suspected distant metastasis.
2. 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.
3. 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)
4. 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.
5. Pregnancy or if the participant does not agree to use an appropriate non-hormonal method of contraception.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
LuminalA	Letrozole 2.5Mg Tab	1. tamoxifen (+ LHRH analogue for premenopausal participant) 2. non-steroidal aromatase inhibitor (+ LHRH analogue for premenopausal participant) 3. Non-steroidal aromatase inhibitor in non-resectable tumor (+ LHRH analogue in premenopausal participant) + CDK4 / 6 inhibitor
Her2 positive	cyclophosphamide	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
LuminalB (Her2 negative)	cyclophosphamide	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
Her2 positive	Letrozole 2.5Mg Tab	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Her2 positive	paclitaxel	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Her2 positive	pertuzumab	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Triple-negative breast cancer	Capecitabine	1. 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) 2. 4x every 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4x docetaxel (90-100mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 ) 3. 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4 times every 2 weeks paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)
LuminalB (Her2 negative)	Letrozole 2.5Mg Tab	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
LuminalA	Tamoxifen	1. tamoxifen (+ LHRH analogue for premenopausal participant) 2. non-steroidal aromatase inhibitor (+ LHRH analogue for premenopausal participant) 3. Non-steroidal aromatase inhibitor in non-resectable tumor (+ LHRH analogue in premenopausal participant) + CDK4 / 6 inhibitor
LuminalA	Goserelin	1. tamoxifen (+ LHRH analogue for premenopausal participant) 2. non-steroidal aromatase inhibitor (+ LHRH analogue for premenopausal participant) 3. Non-steroidal aromatase inhibitor in non-resectable tumor (+ LHRH analogue in premenopausal participant) + CDK4 / 6 inhibitor
LuminalB (Her2 negative)	Tamoxifen	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
LuminalB (Her2 negative)	Goserelin	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
LuminalB (Her2 negative)	Epirubicin	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
LuminalB (Her2 negative)	paclitaxel	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
LuminalB (Her2 negative)	trastuzumab	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
LuminalB (Her2 negative)	Docetaxel	1. 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) 2. 4x 3 weekly E (90-100mg / m˄2) + C (600mg / m˄2), then 1. docetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or 2. 12x weekly paclitaxel (80mg / m˄2) 3. 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then 1. 4 times every 2 weeks with paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) 4. TC: docetaxel (75 mg / m˄2) + cyclophosphamide (600 mg / m˄2) every 21 days with GCSF prevention (6 cycles)
Her2 positive	Tamoxifen	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Her2 positive	Goserelin	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Her2 positive	Epirubicin	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Her2 positive	Docetaxel	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Her2 positive	trastuzumab	1. 4x 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or 2. 4x 3 weekly docetaxel (100mg / m˄2) + trastuzumab +/- pertuzumab 2. 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)
Triple-negative breast cancer	cyclophosphamide	1. 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) 2. 4x every 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4x docetaxel (90-100mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 ) 3. 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4 times every 2 weeks paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)
Triple-negative breast cancer	Epirubicin	1. 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) 2. 4x every 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4x docetaxel (90-100mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 ) 3. 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4 times every 2 weeks paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)
Triple-negative breast cancer	Docetaxel	1. 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) 2. 4x every 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4x docetaxel (90-100mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 ) 3. 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4 times every 2 weeks paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)
Triple-negative breast cancer	paclitaxel	1. 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) 2. 4x every 3 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4x docetaxel (90-100mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 ) 3. 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then 1. 4 times every 2 weeks paclitaxel (175 mg / m˄2) or 2. 12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)

Primary Outcome Measures

Name	Time	Method
pathological complete remission rate	3 year, maximum	no invasive tumor in breast and axilla

Secondary Outcome Measures

Name	Time	Method
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
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 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

Trial Locations

Locations (1)

National Institute of Oncolgy; 🇭🇺 Budapest, Hungary