Epithelial Ovarian Cancer
Conditions
Interventions
TIL for treatment will be cultured from tumor material obtained from primary
surgery, as well as from biopsies . The latter reflect the way tumor material
will be acquired from stage IIb-IIIb patien
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Age * 18 years. * Histologically proven epithelial ovarian cancer. * Recurrent ovarian cancer * Presence of measurable progressive disease according to RECIST version 1.1 or elevated CA125, 2 times the upper normal limit (UNL) within 3 months and confirmed. * Expected survival of at least 3 months. * WHO performance status 0-2. * Within the last 2 weeks prior to study day 0, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified : 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 x the normal upper limit LDH * 2 x the normal upper limit * Viral tests: o Negative for HIV type 1/2, HTLV and TPHA o No HBV (hepatitis B virus) antigen or antibodies against HBc in the serum o No antibodies against HCV (hepatitis C virus) in the serum * 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 PD.
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study for any of the following reasons: * Patients with brain metastases * Clinically significant heart disease (NYHA Class III or IV). * Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or other conditions requiring concurrent medications not allowed during this study. * Active immunodeficiency disease or autoimmune disease requiring immune suppressive drugs. Vitiligo is not an exclusion criterion. * Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma. * Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. * Lack of availability for follow-up assessments. * Pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of this phase I clinical trial is to evaluate the safety and toxicity of Adoptive T cell therapy in combination with IFN* according to CTCAE version 4.0 criteria. For platinum sensitive patients this will be studied in combination with chemotherapy and three cohorts of a reduced dose of IFN*. For these 3 cohorts a phase I design will be followed: If a dose-limiting toxicity (DLT) occurs in one of the three patients within one cohort, then three additional patients will be treated at that dose level. If a DLT occurs in 2/3 or 2/6 patients, the previous dose level will be expanded to at least 6 patients. DLT is defined as follows: Any DLT must be a toxicity that is considered related to study drug. Hematologic * Absolute neutrophil count (ANC) 38.5oC) * Platelets Grade 3 despite optimal loperamide use persisting * 2 weeks * Nausea / vomiting > grade 3 despite optimal use of anti-emetics, persisting * 2 weeks. * Other grade 3 / 4 effects thought to be treatment related | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are the evaluation of a clinical response according to RECIST 1.1 and immune response criteria (irRC), progression free survival (PFS) and overall survival (OS). Clinical benefit is defined as Stable Disease (SD), Partial Response (PR), or Complete response (CR). Additional endpoints are blood CA125 levels and analysis of (induced) immune parameters in patient*s blood and serum, in the T cells used for infusion and in the primary tumor. | — |
Countries
Netherlands
Outcome results
None listed