Recurrent Ovarian Cancer
Conditions
Brief summary
The purpose of this interventional study is to determine the feasibility to combine standard chemotherapy (Carbo/Caelyx or doxorubicin) for recurrent ovarian cancer with immunotherapy (Tocilizumab and Peg-Intron). This study combines standard chemotherapy Carboplatin-Caelyx or doxorubicin with a monoclonal antibody against IL-6R (tocilizumab). High IL-6 levels correlate with poor prognosis and chemoresistance in ovarian cancer patients. In cases of chemoresistant ovarian cancer, therefore, modulation of the IL-6 pathway, by blocking the IL-6 receptor, may represent a promising strategy to both abolish drug resistance and amplify host immunity in patients with recurrent ovarian cancer. Blockade of the IL-6/IL-6R pathway may enhance immunogenic cell death and restore local normal DC maturation. In addition, the use of interferon-alpha (Peg-Intron) allows the full maturation of DC, thereby enhancing the anti-tumor response.
Interventions
DRUGtocilizumab and interferon alpha 2-b
During first three chemotherapy cycles, tocilizumab and/or Peg-Intron are added. Tocilizumab is given in a dose-escalation scheme (1,2,4,8mg/kg n=3) and Peg-Intron is adminstered subcutaneously 1.0ug/kg
DRUGCarboplatin and Caelyx or doxorubicin
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
Sponsors
University Medical Center Groningen
Leiden University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven epithelial ovarian cancer * Progression of disease or relapse after previous therapy with platinum * Measurable disease (RECIST 1.1) or elevated CA125 \> 2 times the upper normal limit (UNL) within 3 months and confirmed * Age ≥18 years * WHO performance status 0-2 * Adequate bone marrow function: WBC ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l * Adequate liver function: bilirubin ≤1.5 x UNL range, ALAT and/or ASAT * 2.5 x UNL (\<5x UNL in case of liver metastases), Alkaline Phosphatase ≤5 x UNL * Adequate renal function: the calculated creatinine clearance should be * 50 mL/min * Survival expectation \> 3 months * Patients must be accessible for treatment and follow-up * Written informed consent according to the local Ethics Committee requirements
Exclusion criteria
* Chemotherapy within past 3 months * Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix * Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias * Known hypersensitivity reaction to any of the components of the treatment * Pregnancy or lactating * Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent * Infection with tuberculosis and hepatitis B or C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron | two years | The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The effect of chemo-immunotherapy on the immune system | two years | Study the effect of chemo-immunotherapy on the immune system by assessing changes in plasma signature (eg IL6, IL8, VEGF, CRP) dendritic cell phenotype and T- and B-cell responses to known tumor antigens in ovarian cancer (eg NY-ESO, p53), antibodies to antigens associated with immunogenic cell death (CRT, HMGB1) and in tumor tissue by gene array |
| The relation between anti-tumor immunity and clinical outcome | two years | Study the relation between anti-tumor immunity and clinical outcome (response (RECIST 1.1), progression free survival (PFS) and overall survival(OS)) |
Countries
Netherlands
Outcome results
None listed