Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Carcinoma, Ductal, Breast

Inflammatory Breast Neoplasms

Carcinoma

Carcinoma, Ductal

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Inflammatory Breast Cancer

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Trastuzumab

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Lapatinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Carboplatin AUC 2 min/mL weekly, infusion will be used as Add-on to the background therapy (same as comparator arm)

background treatment with NLPD (Myocet), Paclitaxel, Herceptin (Trastuzumab fpr Her2 pos), Tyverb (Lapatinib for Her2 pos), Avastin (Bevacizumab for triple negative) agents are used according to marketed formulation via normal procedures at each site and applied according to recommendations of the manufacturers.

Carboplatin, AUC, 2 min/mL weekly, infusion

background treatment according to standards fpr triple negative and Her2pos breast cancer patients Paclitaxel: 80 mg/m² i.v. given weekly on day 1 q day 8 for 18 weeks. NPLD (Myocet®): 20 mg/m² weekly on day 1 q day 8 for 18 weeks Trastuzumab (only for HER2-positive patients): Loading dose: 8 mg/kg, Maintenance dose: 6 mg/kg, day 1 q day 22 for 6 cycles. Post-surgery: up to a total duration of 1 year according to current AGO guidelines Lapatinib 750 mg/day p.o. continuously for 18 weeks; in case of good tolerability (no CTC grade II toxicity except alopecia and nausea/vomiting) during the first cycle the dose may be escalated to 1000 mg.

Bevacizumab: 15 mg/kg i.v., day 1 q day 22 for 6 cycles (only in TNBC patients).

background treatment

Gunter von Minckwitz, MD, Prof

Study participants with primary breast cancer will receive a standard chemotherapy with an anthracycline and a taxane as well as trastuzumab in case of HER2-positive tumors at doses and duration in concordance to current treatment guidelines. Patients will be receive and benefit in addition currently not in the neoadjuvant setting registered medication as lapatinib or bevacizumab of which significant increases of cure (pCR) rates have been reported in previous phase III studies. Patients randomized to carboplatin will receive in addition to the described backbone therapies a potentially active agent which suggested synergy of efficacy with chemotherapies as well as targeted agents. Patients might have the risk of an increase in toxicities due to the added agents and will have additional burden due to investigations required for study participation. However, due to the severity of the underlying disease and the high risk of relapse and death due to the stage of disease, this increase in toxicity and burden appears less relevant compared to the potential higher efficacy and finally cure rate by the incorporated treatments.

Anthracycline/taxane based combination chemotherapy of at least 18 weeks represents the standard of care in the neoadjuvant setting. In HER2-positive disease trastuzumab is given simultaneously to chemotherapy. Recent data from the Neo-Altto and Neosphere trials suggest that a dual blockage of the HER2 receptor with e.g. trastuzumab and lapatinib reach significantly higher pCR rates than trastuzumab alone and should therefore represent the treatment back-bone of new neoadjuvant trials. A preplanned subgroup analysis of the GeparQuinto study demonstrated that in TNBC the addition of bevacizumab resulted in a significant increase of pCR rates (HR 1.4).

Having a better cardiac tolerability profile compared to conventional anthracyclines, the non-pegylated liposomal encapsulated doxorubicin (NPLD) Myocet® might provide the possibility to combine taxane, anthracycline, platinum salt as well with targeted agents as double HER2 blockage or bevacizumab.

Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

A Randomized Phase II Trial Investigating the Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. Surgery takes place shortly after the 18 weeks (six 3-week cycles) chemotherapy treatment. No microscopic evidence of residual viable tumor cells in all resected specimens of the breast and axilla meets the primary endpoint.

To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment in both arms.

LRRFS, RRFS, LRFS, DDFS, IDFS and OS are defined as the time period between registration and first event and will be analyzed after the end of the study by referring to data from GBG patient's registry.

Tolerability and Safety: Descriptive statistics for the 4 treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped

• To assess the pCR rates per arm separately in patients with triple-negative tumors and HER2-positive tumors.

To determine the breast and axilla conservation rate after each treatment.

To determine the pCR rate and local recurrence free survival (LRFS) in patients with a clinical complete response (cCR) and a negative core biopsy before surgery.

To assess the pCR rate in patients with a clinical complete response and a negative core biopsy before surgery.

To assess regional recurrence free survival (RRFS) in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone.

To examine and compare pre-specified molecular markers such as BRCA1-mRNA, P53, ALDH1, p4E-BP1, IL-8 metagene, B-Cell metagene as well as exploratory analyses and lymphocyte infiltration on core biopsies before and surgical tissue after end of chemotherapy. The aim is to identify potential predictive short and long term parameters.

To assess, characterize, and correlate circulating tumor cells and proteins with the effect of treatment.

To correlate Single Nucleotide Polymorphisms (SNPs) of genes with the associated toxicity and histologically assessed treatment effect.

To assess ovarian function measured by amenorrhea rate in correlation with changes in E2, FSH, Anti-Müller Hormone, ultrasound-follicle count in patients aged \<45 years.

Spots Global Cancer Trial Database for background treatment