Denosumab as an add-on Neoadjuvant Treatment (GeparX)

Summary

Pharmacologic inhibition of RANKL attenuates the development of mammary carcinoma and inhibits metastatic progression in multiple mouse models.

In a retrospective analysis it could be demonstrated that elevated expression of RANK was found in 14.5% of patients overall, with a significant predominance in patients with hormone-receptor-negative disease. Expression of RANK was associated with a higher pathological complete response rate but with a shorter disease-free and overall survival. The ABCSG-18 study showed that adjuvant denosumab reduces clinical fractures, improves bone health, and can be administered without added toxicity.

It appears therefore reasonable to test denosumab, a clinically available antibody against RANKL in patients with hormone-receptor-negative primary breast cancer as an adjunct to neoadjuvant chemotherapy for its ability to increase pCR rate and improve outcome in relation to the expression of RANK.

Conditions

• Breast Cancer Female NOS
• Tubular Breast Cancer Stage II
• Mucinous Breast Cancer Stage II
• Invasive Ductal Breast Cancer
• HER2 Positive Breast Cancer
• Inflammatory Breast Cancer
• Tubular Breast Cancer Stage III

Interventions

DRUG

Denosumab

Denosumab 120 mg every 4 weeks for 6 cycles

DRUG

nab-Paclitaxel

nab-paclitaxel 125 mg/m² weekly for 12 weeks or at day 1,8 q22 for 4 cycles (12 weeks)

DRUG

Epirubicin

Epirubicin 90 mg/m² every 2 or 3 weeks for 4 times

DRUG

Cyclophosphamide

Cyclophosphamide 600 mg/m² every 2 or 3 weeks for 4 times

DRUG

Carboplatin

Carboplatin AUC 2 weekly in parallel to nab-Paclitaxel

DRUG

Trastuzumab

Trastuzumab 6 (8) mg/kg every 3 weeks simultaneously to all chemotherapy cycles

DRUG

Pertuzumab

Pertuzumab 420 (840) mg every 3 weeks simultaneously to all chemotherapy cycles

Sponsors & Collaborators

• Amgen

  collaborator INDUSTRY

• Celgene Corporation

  collaborator INDUSTRY

• GBG Forschungs GmbH

  lead OTHER

Principal Investigators

• Jens Uwe Blohmer, MD · Charite Campus Mitte

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-02-13

Primary Completion

2019-12-31

Completion

2020-12-31

Countries

• Germany

Study Locations