NCT01891357

Phase II Trial to Validate Markers for a Response Evaluation of a Combined Therapy in Patients With HER2+ Breast Cancer

A Multicenter Site, Open Label, Phase II Trial to Validate Predictive Markers for the Response Evaluation of a Combined Chemo-immunotherapy in Patients With HER2-positive Early Breast Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: West German Study Group · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The Neo-PREDICT-HER2 Study is phase II trial to validate predictive markers for the response evaluation of a combined chemo-immunotherapy in patients with HER2-positive early breast cancer. The only treatment arm consists of Paclitaxel 80 mg/m2 weekly for 12 weeks with lapatinib 750 mg P.O. daily and trastuzumab 2 mg/kg IV (loading dose 4 mg/kg) weekly for 12 weeks.

Detailed description

Trastuzumab (T)-containing neoadjuvant chemotherapy has been reported to increase the probability of pathological complete response (pCR) in HER2 positive disease up to 67 %. Large trials revealed pCR rates (no remaining invasive and in situ components) of about 30-40 %, if anthracyclines/taxane based polychemotherapy was applied or about 40-45 % if no invasive tumor in the breast and lymph nodes was used as a pCR definition. Nevertheless, resistance to trastuzumab remains one of the most important challenges in adjuvant and metastatic breast cancer therapy causing poor prognosis with an increased incidence of cerebral metastasis and limited therapeutic options after disease progression6. An improvement shows the combination of trastuzumab and lapatinib, which has been reported to have increased efficacy in in-vitro and in metastatic setting in patients who were mostly resistant to both therapies in the previous course of disease. Recent data from the neoadjuvant setting (neoALTTO) - on a paclitaxel backbone - showed a significantly higher pCR rate after L + T than with either compound separately (47 % vs. 20 % and 27.6 % respectively). Several trials are planned to evaluate the combination of both therapies in the adjuvant and neoadjuvant setting. Clinical response measured by sequential evaluation of different proliferation markers (such as Ki-67) following a course of neoadjuvant chemotherapy has been demonstrated to correlate significantly with an increased risk of relapse in patients not achieving pathological complete response. It is therefore clinically relevant to evaluate such proliferation tools for early prediction of combination therapy efficacy (chemotherapy and HER2 targeted therapy). So far, it remains unclear which method of proliferation measurement is the optimal marker for response evaluation regarding a combined chemo-immunotherapy. However, measurement of proliferation and apoptosis genes as well as assessment of changes in Phosphatidylinositol 3-kinases (PI3K), Protein Kinase B (AKT), Insulin-like Growth Factor (IGF) and stem cell signalling after a short course of therapy could provide a unique signature for a dynamic response evaluation. The planned trial will validate predictive markers and a dynamic model based on the sequential evaluation of different proliferation and apoptosis markers. Furthermore it will assess the pCR-rate after 12 weeks of therapy. The aim of the study is to define a predictive marker for the response evaluation of a combined chemo-immunotherapy.

Conditions

• Carcinoma, Ductal, Breast

Interventions

Type	Name	Description
PROCEDURE	Biopsy before and after three weeks of study treatment	Core biopsies for histological analyses, to be analysed by the central pathology
DRUG	paclitaxel
DRUG	lapatinib
DRUG	trastuzumab

Timeline

• Start date: 2013-09-30
• Primary completion: 2016-11-16
• Completion: 2016-11-16
• First posted: 2013-07-03
• Last updated: 2019-09-17
• Results posted: 2019-09-17

Locations

10 sites across 1 country: Germany