NCT03894007

Improving Pre-operative Systemic Therapy for Human Epidermal Growth Factor Receptor 2 (HER2) Amplified Breast Cancer

Improving Pre-operative Systemic Therapy for Human Epidermal Growth Factor Receptor 2 (HER2) Amplified Breast Cancer Part of a Platform of Translational Phase II Trials Based on Molecular Subtypes

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Renske Altena · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 2 study evaluating medical treatment before surgery in HER2-amplified early breast cancer patients. Patients receive chemotherapy with HER2-targeted antibodies and are randomised to receive the checkpoint inhibitor atezolizumab or not.

Detailed description

The primary aim is to investigate whether the rate of pCR, after optimal neoadjuvant anti-HER2 based systemic therapy, can be increased by addition of atezolizumab. Secondary aims are to assess safety and tolerability of this treatment combination, and to identify therapy predictive factors for the anti-HER2 monoclonal antibodies trastuzumab and pertuzumab plus-minus atezolizumab with a backbone of chemotherapy, using modern molecular biological investigational procedures with analyses by repeated biopsies from an intra-patient longitudinal study design.

Conditions

• Early-stage Breast Cancer
• HER2-positive Breast Cancer

Interventions

Type	Name	Description
DRUG	Docetaxel	75 mg/m2 iv, escalated to 100 mg/m2 if tolerated, day 1 every third week, 4 courses preoperatively.
DRUG	Carboplatin	AUC 6 iv, day 1 every third week, 4 courses preoperatively.
DRUG	Trastuzumab	600 mg sc, day 1 every third week, 4 courses preoperatively. 14 courses postoperatively if complete response.
DRUG	Pertuzumab	840 mg iv starting dose, thereafter 420 mg, day 1 every third week. 14 courses postoperatively if complete response in patients with baseline high risk tumours.
DRUG	Epirubicin	90 mg/m2 iv, escalated to 100 mg/m2 if tolerated, day 1 every third week, 3 courses preoperatively
DRUG	Cyclophosphamide	600 mg/m2 iv, day 1 every third week, 3 courses preoperatively
DRUG	Atezolizumab	840 mg iv, day 1 every third week, 3 courses preoperatively if randomised to arm A.
DRUG	Trastuzumab emtansine	3.6 mg/kg iv, day 1 every third week, 14 courses postoperatively if not complete response.
DRUG	Paclitaxel	80 mg/m2 iv, day 1 weekly, 12 weeks (4 cycles), in case of (anticipated) unmanageable toxicity related to docetaxel.

Timeline

• Start date: 2019-05-23
• Primary completion: 2021-06-30
• Completion: 2021-06-30
• First posted: 2019-03-28
• Last updated: 2021-09-23

Locations

8 sites across 1 country: Sweden

Regulatory

• FDA-regulated drug study