1 Det Sundhedsvidenskabelige Fakultet, SDU2 Clinical Pathology, Institute of Regional Health Research, Det Sundhedsvidenskabelige Fakultet, SDU3 Department of Oncology, Institute of Regional Health Research, Det Sundhedsvidenskabelige Fakultet, SDU4 unknown5 Department of Oncology, Institute of Regional Health Research, Det Sundhedsvidenskabelige Fakultet, SDU6 Clinical Pathology, Institute of Regional Health Research, Det Sundhedsvidenskabelige Fakultet, SDU
Background: Currently, randomized trials support the use of either pegylated liposomal doxorubicin (PLD) or topotecan as second-line therapy in women with recurrent platinum-resistant ovarian cancer (OC). However, patients with platinum-resistant recurrent OC have few therapeutic options and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). Results in colorectal cancer have clearly indicated that KRAS mutant tumors do not respond to treatment with EGFR inhibitors. To date, panitumumab has been evaluated in combination with chemotherapy in patients with colorectal, lung, and head and neck cancer. No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. Methods: Eligibility criteria are confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end of first or second line platinum-based chemotherapy. Only patients with maximum 2 prior lines of chemotherapy, measurable disease by CA125 criteria and with KRAS wild type are eligible. Patients are treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m2 day 1, every 4 weeks. Tumor assessment is performed at baseline and at every third cycle according to CA-125 criteria. The trial is based on Simon's two-stage minimax design with a division into two steps. 18 patients are included in the first step. If 4 responses or fewer are seen the trial is terminated. Otherwise accrual continues to a total of 33 patients. At present, 15 patients have been enrolled. The primary endpoint is to investigate the response rate in platinum-resistant, KRAS wild- type OC patients treated with PLD supplemented with panitumumab. Translational research is included as a secondary endpoint and tumor tissue/blood samples are collected as part of the trial.