NCT02339532

Neoadjuvant Phase II Trial in Patients With T1c Operable, HER2-positive Breast Cancer According to TOP2A Status

Neoadjuvant Phase II Trial Combining [3 FEC 100 Followed by 3 Docetaxel Associated With Trastuzumab Plus Pertuzumab] or [6 Docetaxel, Carboplatin Associated With Trastuzumab Plus Pertuzumab] According to TOP2A Status in Patients With T1c Operable, HER2-positive Breast Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 86 (actual)
• Sponsor: UNICANCER · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main objective of this multicenter study will therefore be to evaluate pathologic complete response rates of an anthracycline-based regimen \[FEC 100 - TAXOTERE® - HERCEPTIN® - PERTUZUMAB\] and a non anthracycline-based regimen \[TAXOTERE® - CARBOPLATINE - HERCEPTIN® - PERTUZUMAB\] according to the presence or not of TOP2A gene amplification in a population of breast cancer patients with HER2 overexpression. A very important objective of the study will be the evaluation of biomarkers that predict response to treatment.

Detailed description

In this phase II study, we propose a treatment strategy that not only takes advantage of the complementary action of trastuzumab and pertuzumab but also the relevance of an anthracycline-based regimen. Indeed, besides the cardiac toxicity that can be induced by these three agents, anthracycline chemotherapy may not confer benefit to all patients. The underlying scientific hypothesis is based on data from the NEOSPHERE neoadjuvant trial showing that addition of pertuzumab to trastuzumab plus docetaxel improved the pCR rate (46% versus 29% without pertuzumab) in T2-T3 tumors. Therefore, we hypothesize that for smaller tumors (T1c), the pCR rate should be higher, on the order of 60% in patients with the coamplification (with anthracycline therapy) and 55% for the group without coamplification (without anthracycline therapy). The sample size of 90 patients (45 per group) planned for the phase II study will allow 15% precision with the expected pCR rates of 60% (95%CI: 45%-75%) for patients with coamplification and 55% (95%CI: 40%-70%) for those without coamplification. In addition, exploratory analyses will aim to identify predictive markers of pCR in order to target biologically defined subpopulations in which pCR rates might even be higher.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	FEC100	3 cycles of FEC 100 administered IV q3w * 5-Fluorouracil (5-FU) 500 mg/m² * Epirubicin 100 mg/m² * Cyclophosphamide 500 mg/m²
DRUG	Docetaxel	TOP2A amplified : DOCETAXEL 75 mg/m² IV escalating at 100 mg/m² IV as tolerated q3w TOP2A not amplified : DOCETAXEL 75 mg/m² IV
DRUG	Trastuzumab	Trastuzumab 8 mg/kg loading dose administered intravenously (IV) followed by 6 mg/kg IV q3w in subsequent cycles.
DRUG	Pertuzumab	Pertuzumab 840 mg loading dose administered IV followed by 420 mg IV q3w in subsequent cycles.
DRUG	Carboplatin	CARBOPLATIN AUC 6 IV q3w

Timeline

• Start date: 2015-01-01
• Primary completion: 2019-10-07
• Completion: 2024-07-08
• First posted: 2015-01-15
• Last updated: 2024-11-08

Locations

12 sites across 1 country: France