Background: Response rates for 2^nd line therapies in recurrent platinum resistant ovarian cancer (PROC) are low, and ex-vivo assays do not reliably predict individual response. To improve response rates to 2^nd line agents, clinical trial MC1463 (#NCT02312245) uses patient-derived xenografts (PDX or Avatars) to assign therapy based on the matched Avatar in vivo response. Our experience confirms platinum response correlation between patients and Avatars (1); however a predictive assay for PROC will be more clinically relevant given the time required for Avatar development and recurrence pattern of ovarian cancer. Methods: Tumor collected from consenting patients is injected into immunodeficient mice. After tumor expansion, Avatars are treated with intraperitoneal (IP) carboplatin/paclitaxel (Phase 1) prior to randomization to additional IP treatment (Phase 2) with gemcitabine, topotecan, paclitaxel, or liposomal doxorubicin for 28 days. Change in tumor diameter is quantitated by ultrasound. To maintain confidentiality, a user-limited web-based portal links clinicians to Avatar development progress. Prior to treatment for platinum resistant recurrence, defined as measurable or non-measurable disease (including persistently elevated CA-125) within 6 months of completing of a platinum-based regimen, patients consent to pre-registration, and the most effective therapy is chosen by an Avatar tumor board composed of medical oncologists, biostatisticians, and lab scientists. Avatar drug performance is assessed graphically and via linear mixed models and non-parametric methods. Both Avatar and patient factors are considered by the board. The patient is then registered and treated with the assigned regimen. Patients are excluded for Avatar engraftment failure, prior cytotoxic therapy for PROC, poor performance status, or concurrent cancer. Primary endpoint is percentage of patients with response to assigned therapy based on RECIST criteria. Secondary endpoints include PFS, OS, and adverse events. Currently, 114 Avatars are in progress, and Phase 1 and 2 are complete for 27 and 18 models, respectively. One patient has been enrolled and randomized to Avatar-directed chemotherapy.

Weroha SJ et al. Clin Cancer Res. 2014.