TIL Therapy in Combination With Checkpoint Inhibitors for Metastatic Ovarian Cancer
Condition: Metastatic Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved
      impressive clinical results with durable complete responses in patients with metastatic
      melanoma. Recently, the investigators have completed a pilot study treating 6 patients with
      metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by
      in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients
      receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After
      TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in
      vivo.

      The investigators recent pilot study has shown TIL therapy in patients with metastatic
      ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where
      observed and therefore the investigators plan to combine TIL therapy with checkpoint
      inhibitors to potentially increase the clinical effect.
    

Detailed description: 
      Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved
      impressive clinical results with durable complete responses in patients with metastatic
      melanoma. Recently, the investigators have completed a pilot study treating 6 patients with
      metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by
      in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients
      receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After
      TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in
      vivo.

      The investigators recent pilot study has shown TIL therapy in patients with metastatic
      ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where
      observed and therefore the investigators plan to combine TIL therapy with checkpoint
      inhibitors to potentially increase the clinical effect.

      Objectives:

      To evaluate safety and feasibility when treating patients with metastatic ovarian cancer with
      ACT with TILs in combination with checkpoint inhibitors.

      To evaluate treatment related immune responses To evaluate clinical efficacy

      Design:

      Patients will be screened with a physical exam, medical history, blood samples and ECG.

      Patients will be treated with one dose of Ipilimumab 14 days before undergoing surgery to
      harvest tumor material for TIL production. Patients is admitted on day -8 in order to undergo
      lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. On day -2
      patients will start treatment with Nivolumab every 2 weeks for a total of 4 doses to increase
      the activity of the infused TIL product.

      On day 0 patients receive TIL infusion and shortly after starts IL-2 stimulation with a daily
      subcutaneous dose for a total of 14 days.The patients will followed until progression or up
      to 5 years.
    

Intervention name(s): Cyclophosphamide; Fludarabine; TIL infusion; Interleukin-2; Ipilimumab; Nivolumab
Intervention type(s): Drug; Drug; Biological; Drug; Drug; Drug
Intervention description(s): Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.; Fludarabine 25 mg/m2 is administered on day -5 to day -1.; The maximum number of expanded TILs are infused over 30-45 minutes on day 0.; Interleukin-2 is administered as a daily low-dose subcutaneous injection of 2 MIU for a total of 14 days.; One dose of Ipilimumab 3 mg/kg is administered 14 days prior to surgical removal of tumor tissue for TIL expansion.; Nivolumab 3 mg/kg is administered on day -2 before TIL infusion and every 2 weeks for a total of 4 doses.
Other intervention name(s): Fludarabine phosphate; TILs; IL-2
Intervention MeSH terms: Cyclophosphamide; Nivolumab; Fludarabine; Fludarabine phosphate; Ipilimumab; Interleukin-2
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment