NCT01835236

Trastuzumab & Pertuzumab Followed by T-DM1 in MBC

A Randomized Phase II Trial of Pertuzumab in Combination With Trastuzumab With or Without Chemotherapy, Both Followed by T-DM1 in Case of Progression, in Patients With HER2-positive Metastatic Breast Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 208 (actual)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In HER2-positive metastatic breast cancer, trastuzumab based treatment is the standard of care as long as there are no contraindications to trastuzumab. Frequently, trastuzumab is being combined with taxanes in the first-line setting. However, since therapy with trastuzumab is active even in the absence of chemotherapy in HER2-positive MBC, the optimal treatment strategy either in combination or in sequence with chemotherapy is still under debate. This randomized phase II trial is studying a new strategy for the treatment of metastatic breast cancer with HER2-positive. First-line treatment consists of trastuzumab and pertuzumab, a treatment without chemotherapy. In case of disease progression, chemotherapy with T-DM1 is then performed as second-line treatment. Third-line and further line therapies are performed according to the physician's discretion. If this new therapeutic strategy is as effective and better tolerated than the conventional strategy, this would mean a serious breakthrough in the treatment of HER2-positive metastatic breast cancer.

Detailed description

OBJECTIVES: Primary -To evaluate the efficacy in terms of overall survival (OS) at 24 months of a chemotherapy-free dual HER2-inhibition with trastuzumab and pertuzumab (first-line) followed by T-DM1 (second-line) and of a chemotherapy-containing dual HER2-inhibition with trastuzumab and pertuzumab (first-line) followed by T-DM1 (second-line) in patients with HER2-positive metastatic breast cancer. Secondary * To evaluate other efficacy parameter * To evaluate the safety and tolerability profile of the two treatment strategies * To evaluate the Quality of Life (QoL) * To learn how patients are treated after trial treatment OUTLINE: This is a multicenter study. Patients are stratified according to hormone receptor status (positive vs negative), prior trastuzumab (never or \>12 months vs ≤12 months after last infusion), visceral metastases (present vs absent) and site. Patients are randomized to 1 of 2 treatment arms.

Conditions

• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab	First administration (loading dose) 8 mg/kg i.v. infusion over 90 min. \- then every 3 weeks until progression 6 mg/kg i.v. infusion over 30 to 90 min.
DRUG	Pertuzumab	First administration (loading dose) 840 mg i.v. infusion over 60 min. \- then every 3 weeks until progression 420 mg i.v. infusion over 30 to 60 min.
DRUG	Paclitaxel	Day 1, 8 and 15; every 4 weeks for ≥4 months 90 mg/m2 i.v. infusion
DRUG	Vinorelbine	First administration: Day 1 and 8 25 mg/m2 i.v. infusion * then day 1 and 8, every 3 weeks for ≥4 months 30 mg/m2 i.v. infusion
DRUG	T-DM1	Every 3 weeks until unacceptable toxicity or progressive disease is observed 3.6 mg/kg i.v. infusion First dose: over 90 min (± 10 min.) Subsequent doses: over 30 min. (± 10 min.)

Timeline

• Start date: 2013-03-03
• Primary completion: 2018-01-11
• Completion: 2020-05-26
• First posted: 2013-04-18
• Last updated: 2021-03-30

Locations

71 sites across 4 countries: France, Germany, Netherlands, Switzerland