Status and phase
Conditions
Treatments
About
The clinical benefit of standard treatment for patients with epithelial ovarian cancer (EOC) are poor. Ovarian cancer is a highly immunogenic tumor and good survival is tightly linked to the presence of tumor-infiltrating CD8+ T cells and the absence of immunosuppressive immune cells. This clear correlation between T cell infiltration and disease progression suggests that EOC may be sensitive to adoptive cell therapy by infusion of ex-vivo expanded autologous Tumor Infiltrating Lymphocytes (TIL) provided that immune suppression is reduced. Carboplatin+paclitaxel chemotherapy is directly killing tumor cells but was also shown to alleviate immunosuppression for 2 weeks coinciding with enhanced T-cell immunity, potentially creating a window of opportunity for T-cell based immunotherapy.
In addition, there is evidence that interferon alpha (IFNα) not only may work as a low toxic preconditioning regimens that creates the space required for the infused TIL but that it also supports the TIL by sustaining their persistence and indirectly their function, by upregulation of HLA class I on tumor cells and decreasing the numbers of regulatory T cells. Based on this we hypothesize that a synergistic clinical effect may be obtained when adoptive cell therapy with autologous TIL is administered during treatment with chemotherapy and IFNα. The feasibility and safety of TIL administration is studied in the window of opportunity created by carboplatin-paclitaxel chemotherapy with or without interferon alpha (IFNα). Furthermore, exploratory studies will be performed to analyze and confirm the proposed underlying mechanisms.
Tumor material for TIL production will be collected during first line debulking surgery in case of FIGO stage IIIC/IV disease (pre-OVACURE) or in case of recurrent platinum sensitive disease an extra biopsy can be planned (OVACURE).
Full description
Study the feasibility and safety of TIL administration in the window of opportunity created by carboplatin-paclitaxel chemotherapy with or without interferon alpha (IFNα). Furthermore, exploratory studies will be performed to analyze and confirm the proposed underlying mechanisms.
Intervention:
Cohort 1
Cohort 2
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Lab Parameter Range Hemoglobin ≥ 6,0 mmol/l Granulocytes ≥ 1,500/µl Lymphocytes ≥ 700/µl Platelets ≥ 100,000/µl Creatinine clearance ≥ 50 min/ml Serum bilirubin ≤ 40 mol/l ASAT and ALAT ≤ 5 times the normal upper limit LDH ≤ 2 times the normal upper limit
Viral tests:
Able and willing to give valid written informed consent.
Prior treatment, including immunotherapy e.g. with anti-PD(L)1, is allowed but systemic therapy and radiotherapy must have been discontinued for at least two weeks before study entry.
Patients should have disease progression.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
12 participants in 2 patient groups
Loading...
Central trial contact
Judith Kroep, MD, PhD; Els Verdegaal, PhD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal