Ovarian Serous Adenocarcinoma

This phase II trial studies the effect of APL-2 when given in combination with either pembrolizumab or pembrolizumab and bevacizumab compared with bevacizumab alone in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent) and a buildup of fluid and cancer cells (malignant effusion). APL-2 may limit tumor progression, decrease malignant effusion production, and improve the immune system's response against cancer cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving APL-2 together with either pembrolizumab or pembrolizumab and bevacizumab may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer and malignant effusion compared to bevacizumab alone.

This phase III trial compares minimally invasive surgery (MIS) to laparotomy in treating patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who are receiving chemotherapy before and after surgery (neoadjuvant chemotherapy). MIS is a surgical procedure that uses small incision(s) and is intended to produce minimal blood loss and pain for the patient. Laparotomy is a surgical procedure which allows the doctors to remove some or all of the tumor and check if the disease has spread to other organs in the body. MIS may work the same or better than standard laparotomy after chemotherapy in prolonging the return of the disease and/or improving quality of life after surgery.

This phase I trial studies the side effects of hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery in treating patients with stage III or IV ovarian, fallopian tube or peritoneal cancer receiving chemotherapy before surgery. Hyperthermic intraepithelial chemotherapy involves the infusion of heated cytotoxic chemotherapy that circulates into the abdominal cavity at the time of surgery. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hyperthermic intraepithelial chemotherapy with cisplatin after surgery or cisplatin before surgery may kill more tumor cells compared to usual care.

Background: Advanced ovarian cancer is a highly dangerous disease, and many patients lose their lives due to limited treatment effectiveness. Previous studies have shown that current immunotherapy (e.g., PD-1 inhibitors) has poor results in ovarian cancer. The research team discovered that adding "heated abdominal chemotherapy" (called HIPEC, which uses a heated drug solution to wash the abdomen) to standard chemotherapy helps patients better control tumors. Recent lab studies also found that HIPEC not only reduces "harmful cells" around tumors that block drug effectiveness but also makes immunotherapy drugs work better. Animal experiments further confirmed that combining HIPEC with immunotherapy improves outcomes. Therefore, the investigators aim to test a key question: Can HIPEC help immunotherapy drugs work more effectively in humans? Study Details: The study will conduct a small two-phase trial, planning to enroll 30 patients with advanced ovarian cancer (Stage IIIc-IVA). All participants will receive standard chemotherapy (paclitaxel + platinum drugs) combined with HIPEC and an immunotherapy drug (tislelizumab, a PD-1 inhibitor). The main goal is to check whether tumors are completely removed after surgery. Investigators will also track how long tumors stay under control, overall survival time, treatment safety, and use blood and tumor tissue tests to find biomarkers that predict treatment response. Why This Matters: The study hopes to identify a safe method to enhance immunotherapy effectiveness and offer improved outcomes for advanced ovarian cancer patients.