This randomized phase II trial studies how well carboplatin and paclitaxel with or without trastuzumab works in treating patients with human epidermal growth factor receptor 2 (HER2)-positive stage III-IV uterine cancer or uterine cancer that has come back (recurrent). Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. It is not yet known whether carboplatin and paclitaxel are more effective when given with or without trastuzumab in treating uterine cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01367002.
PRIMARY OBJECTIVE:
I. To estimate whether the addition of trastuzumab to paclitaxel and carboplatin chemotherapy improves progression free survival (PFS) when compared to paclitaxel and carboplatin alone in uterine serous papillary carcinoma (USPC) patients overexpressing HER2/neu at 3+ level by immunohistochemistry (IHC) or positive by fluorescent in situ hybridization (FISH).
SECONDARY OBJECTIVES:
I. To assess objective response rate (ORR).
II. To assess overall survival (OS).
III. To assess the safety profile of trastuzumab in USPC patients.
EXPLORATORY/CORRELATIVE OBJECTIVES:
I. To determine peripheral blood natural killer (NK) cell numbers and activity in HER2/neu+ USPC patients to provide a basis for assessing the possible therapeutic contributions of immune mechanisms of action of trastuzumab.
II. To study HER2/neu extracellular domain (ECD) circulating levels in the plasma of USPC patients overexpressing HER2/neu before, during and after treatment to elucidate whether changes in HER2/neu ECD would predict response to trastuzumab.
III. To determine whether cancer antigen 125 (CA-125) levels correlate with disease activity in advanced and/or recurrent disease.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive paclitaxel and carboplatin as in Arm A and trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue to receive cycles of trastuzumab indefinitely in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Lead OrganizationYale University
Principal InvestigatorAlessandro D. Santin
