Neoadjuvant Treatment of Breast Cancer

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: Tamoxifen; Drug: Goserelin; Drug: Letrozole 2.5Mg Tab; Drug: Epirubicin; 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 Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: gabor Rubovszky; Phone Number: 3442 +3612248600; Email: garub@oncol.hu
• Study Contact Backup: Name: Balazs Madaras; Phone Number: +3612248600; Email: madarasb@oncol.hu

Study Locations

• Hungary
  • Budapest, Hungary, 1122
    • National Institute of Oncolgy
    • Contact: Gabor Rubovszky, Ph D; Phone Number: 3442 +3612248600; Email: garub@oncol.hu
    • Contact: Balazs Madaras; Phone Number: +3612248600; Email: madarasb@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Breast cancer patients for whom neoadjuvant therapy is proposed by multidisciplinary team

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	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), thendocetaxel (90-100 mg / m˄2) 4 times in every 3 weeks or12x weekly paclitaxel (80mg / m˄2); 4x every 2 weeks Epirubicin (E) (90-100mg / m˄2) + Cyclophosphamid (C) (600mg / m˄2), then4 times every 2 weeks with paclitaxel (175 mg / m˄2) or12x 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: cyclophosphamide; chemotherapy; Drug: Tamoxifen; endocrine therapy; Drug: Goserelin; endocrine therapy; Drug: Letrozole 2.5Mg Tab; endocrine therapy; Other Names: letrozole; Drug: Epirubicin; 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), then12 times weekly paclitaxel + trastuzumab (every week or 3 weekly) +/- pertuzumab (3 weekly) or4x 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: cyclophosphamide; chemotherapy; Drug: Tamoxifen; endocrine therapy; Drug: Goserelin; endocrine therapy; Drug: Letrozole 2.5Mg Tab; endocrine therapy; Other Names: letrozole; Drug: Epirubicin; 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), then4x docetaxel (90-100mg / m˄2) or12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2 ); 4x every 2 weeks E (90-100mg / m˄2) + C (600mg / m˄2), then4 times every 2 weeks paclitaxel (175 mg / m˄2) or12x weekly paclitaxel (80mg / m˄2) +/- carboplatin (AUC2)	Drug: cyclophosphamide; chemotherapy; Drug: Epirubicin; chemotherapy; Drug: Docetaxel; chemotherapy; Drug: paclitaxel; chemotherapy; Drug: Capecitabine; chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete remission rate	no invasive tumor in breast and axilla	3 year, maximum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
invasive disease-free survival	from the beginning of neoadjuvant therapy to the first appearance of invasive tumor or death	10 years
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	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	4 years
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ BR45)	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	4 years
evaluation of side effects	to collect information all potential complaints and adverse event during and after treatment	10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
dose density assessment	actual dose / planned dose	3 year, maximum
investigate the potential prognostic effect of neutrophil/lymphocyte ratio	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	10 years
investigate the potential prognostic effect of monocyte/lymphocyte ratio	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	10 years
investigate potential prognostic factors, CRP	C-reactive protein serum level befor start of chemotherapy	10 years
investigate potential prognostic factors	circulating free-DNA at baseline, before 3. cycle, before surgery	10 years

Collaborators and Investigators

• Sponsor: National Institute of Oncology, Hungary
• Investigators: Principal Investigator: Gabor Rubovszky, NIO Hungary

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): December 1, 2031

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: November 20, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 20, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Neoadjuvant systemic therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Docetaxel; Cyclophosphamide; Trastuzumab; Capecitabine; Epirubicin; Letrozole; Goserelin; Tamoxifen; Pertuzumab
• Other Study ID Numbers: PANONC-1 Version: 1.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The individual participant data are not planned to be shared with other researchers but will be available upon request except personal data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No