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)
Overview
- Phase
- Phase 2
- Intervention
- Trastuzumab
- Conditions
- Breast Neoplasms
- Sponsor
- US Oncology Research
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female, Age ≥ 18 years
- •Histologic or cytologic confirmation of human epidermal growth factor receptor 2 (HER2)-positive breast cancer according to most recent biopsy (local testing permitted)
- •Measurable or evaluable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1)
- •Previous treatment with ado-trastuzumab emtansine (T-DM1) for metastatic disease
- •a. Prior therapy with pertuzumab is allowed but not required
- •At least 1 but no more than 3 prior chemotherapy regimens for metastatic breast cancer (MBC)
- •Life expectancy \> 6 months
- •Eastern Cooperative Group (ECOG) performance status ≤ 2
- •Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA) and within normal limits per institutional guidelines
- •Adequate bone marrow function as indicated by the following:
Exclusion Criteria
- •Patients will be excluded from the study based on the following criteria:
- •Prior treatment in the metastatic setting with the agent chosen as physician's choice of chemotherapy
- •Active infection
- •Uncontrolled central nervous system metastases, defined as clinical or radiologic evidence of progression of brain metastases or clinical signs of leptomeningeal disease
- •a. Patients with treated brain metastases are eligible provided they do not have clinical or radiologic evidence of disease progression and have been off of dexamethasone for at least 3 weeks
- •Patient is pregnant or lactating
- •Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)
- •Prior radiation therapy within the last 2 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation).
- •Requirement for chronic steroid therapy with a requirement for \> 5mg/day of prednisone or the equivalent.
- •a. Treatment with physiologic doses of hydrocortisone up to 20 mg daily (QD) is allowed.
Arms & Interventions
Triple Therapy
Physician's choice of chemotherapy plus trastuzumab plus pertuzumab * trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND * physician's choice of chemotherapy: 1. Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR 2. Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR 3. Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR 4. Docetaxel 75 mg/m2 IV every 3 weeks; OR 5. Capecitabine 1500 mg by mouth twice a day (PO BID) 14 days on and then 7 days off. * AND pertuzumab given as a loading dose of 840 mg IV on Day 1 followed by 420 mg IV every 3 weeks.
Intervention: Trastuzumab
Triple Therapy
Physician's choice of chemotherapy plus trastuzumab plus pertuzumab * trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND * physician's choice of chemotherapy: 1. Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR 2. Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR 3. Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR 4. Docetaxel 75 mg/m2 IV every 3 weeks; OR 5. Capecitabine 1500 mg by mouth twice a day (PO BID) 14 days on and then 7 days off. * AND pertuzumab given as a loading dose of 840 mg IV on Day 1 followed by 420 mg IV every 3 weeks.
Intervention: Pertuzumab
Triple Therapy
Physician's choice of chemotherapy plus trastuzumab plus pertuzumab * trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND * physician's choice of chemotherapy: 1. Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR 2. Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR 3. Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR 4. Docetaxel 75 mg/m2 IV every 3 weeks; OR 5. Capecitabine 1500 mg by mouth twice a day (PO BID) 14 days on and then 7 days off. * AND pertuzumab given as a loading dose of 840 mg IV on Day 1 followed by 420 mg IV every 3 weeks.
Intervention: Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine
Double Therapy
Physician's choice of chemotherapy plus trastuzumab * trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND * physician's choice of chemotherapy: 1. Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR 2. Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR 3. Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR 4. Docetaxel 75 mg/m2 IV every 3 weeks; OR 5. Capecitabine 1500 mg PO BID 14 days on and then 7 days off.
Intervention: Trastuzumab
Double Therapy
Physician's choice of chemotherapy plus trastuzumab * trastuzumab, given as a loading dose of 8 mg/kg intravenously (IV, or through the vein) on Day 1 followed by 6 mg/kg IV every 3 weeks thereafter, AND * physician's choice of chemotherapy: 1. Vinorelbine 25 mg/m2 IV weekly times 3 with 1 week off; OR 2. Paclitaxel 80 mg/m2 IV weekly times 3 with 1 week off; OR 3. Nab-Paclitaxel 100 mg/m2 IV weekly times 3 with 1 week off; OR 4. Docetaxel 75 mg/m2 IV every 3 weeks; OR 5. Capecitabine 1500 mg PO BID 14 days on and then 7 days off.
Intervention: Vinorelbine, Paclitaxel, Nab-Paclitaxel , Docetaxel, Capecitabine
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: 2 years
The primary objective of this study is to compare progression-free survival (PFS \[also known as time to disease progression\]) with the addition of pertuzumab to trastuzumab plus physician's choice of chemotherapy versus trastuzumab plus physician's choice of chemotherapy in patients who have previously received treatment with ado-trastuzumab emtansine (TDM1) for HER2+ metastatic breast cancer.
Secondary Outcomes
- Number of adverse events and serious adverse events(2 years)
- Progression-free survival (PFS) in patients (pts) with prior pertuzumab(2 years)
- Number of patients with complete and partial responses(2 years)
- Overall survival(2 years)
- Progression-free survival (PFS) in pts with prior chemotherapy(2 years)