NCT02229149

Phase 2 Study of Standard Chemotherapy With Trastuzumab, Plus or Minus Pertuzumab, for Pre-treated Metastatic Breast Cancer

Randomized Phase II Trial of Chemotherapy of Physician's Choice Plus Trastuzumab Versus Chemotherapy of Physician's Choice Plus Trastuzumab Plus Pertuzumab In Women With Pretreated, HER2-Overexpressing Metastatic Breast Cancer (MBC)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: US Oncology Research · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase 2 study will seek to determine the effectiveness of chemotherapy (physician's choice of vinorelbine, taxane \[paclitaxel, docetaxel or nab paclitaxel\] or capecitabine) plus trastuzumab vs chemotherapy (physician's choice) plus trastuzumab plus pertuzumab in women with HER2-overexpressing metastatic breast (MBC) that has been previously treated with ado-trastuzumab emtansine (T-DM1) in the metastatic setting.

Detailed description

The current preferred first-line therapy for patients with HER2-overexpressing metastatic breast cancer (MBC) is a taxane plus trastuzumab plus pertuzumab, based on results from the CLEOPATRA trial. For patients with disease that has progressed on trastuzumab and a taxane, ado-trastuzumab emtansine (T-DM1) was recently approved based on results from the EMILIA trial showing superiority in this setting compared with capecitabine plus lapatinib. However, the standard for first-line therapy may change again in the near future, when results become available from the MARIANNE trial, which is evaluating T-DM1 alone or in combination with pertuzumab as upfront therapy. Two important questions that may be raised by the findings of this study are whether pertuzumab is effective as second- or later-line therapy following single-agent T-DM1, and whether pertuzumab administered beyond progression on prior pertuzumab therapy is of clinical benefit as trastuzumab has been proven to be. The study will seek to determine the efficacy of chemotherapy (physician's choice of vinorelbine, taxane \[paclitaxel, docetaxel or nab paclitaxel\] or capecitabine) plus trastuzumab vs chemotherapy (physician's choice) plus trastuzumab plus pertuzumab in women with HER2-overexpressing MBC that has been previously treated with T-DM1 in the metastatic setting. We hypothesize that the addition of pertuzumab to trastuzumab plus chemotherapy will improve median progression-free survival (PFS), compared to trastuzumab plus chemotherapy alone, as second- or later-line therapy in patients who have received prior T-DM1. Patients will be stratified according to whether they have received prior pertuzumab versus not. We will also explore whether continuing treatment with pertuzumab in patients who have been previously treated with pertuzumab improves PFS.

Conditions

• Breast Neoplasms
• Malignant Tumor of the Breast

Interventions

Type	Name	Description
DRUG	Trastuzumab	Treatment for all patients will consist of trastuzumab, given as a loading dose of 8 mg/kg IV on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter. Patients randomized to the chemotherapy plus trastuzumab arm (without pertuzumab) can receive trastuzumab 6 mg/kg IV every 3 weeks if they are receiving docetaxel or capecitabine on a 3-week cycle, or 4 mg/kg IV every 2 weeks if they are receiving vinorelbine, paclitaxel, or nab-paclitaxel on a 4-week cycle. The loading dose for all patients remains 8 mg/kg. For patients randomized to the chemotherapy plus trastuzumab plus pertuzumab arm, both trastuzumab and pertuzumab need to be administered every 3 weeks regardless of which chemotherapy agent they are receiving.
DRUG	Pertuzumab	pertuzumab given as a loading dose of 840 mg IV on Day 1 followed by 420 mg IV every 3 weeks.
DRUG	Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine	physician's choice of chemotherapy: * Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR * Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR * Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR * Docetaxel 75 mg/m2 IV every 3 weeks; OR * Capecitabine 1500 mg by mouth twice a day (PO BID) 14 days on and then 7 days off.

Timeline

• Start date: 2014-12-01
• Primary completion: 2022-01-01
• Completion: 2022-01-01
• First posted: 2014-08-29
• Last updated: 2022-12-02

Locations

1 site across 1 country: United States