Chemo-Immunotherapy: Observational Trial of Carboplatin-pegylated Liposomal Doxorubicin (PLD) or Doxorubicin Combination Chemotherapy With Tocilizumab, a Humanized Monoclonal Antibody Against the Human Interleukin-6 (IL-6) Receptor, and Pegylated Interferon Alpha (Peg-Intron) for Patients With Recurrent Ovarian Cancer.
Overview
- Phase
- Phase 1
- Intervention
- Carboplatin and Caelyx or doxorubicin
- Conditions
- Recurrent Ovarian Cancer
- Sponsor
- Leiden University Medical Center
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron
- Status
- Completed
- Last Updated
- 10 years ago
Overview
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.
Investigators
J.R. Kroep
MD, PhD
Leiden University Medical Center
Eligibility Criteria
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
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
Arms & Interventions
Group 1
Carboplatin/Caelyx
Intervention: Carboplatin and Caelyx or doxorubicin
Group 2
Carboplatin/Caelyx or doxorubicin plus Tocilizumab
Intervention: tocilizumab and interferon alpha 2-b
Group 2
Carboplatin/Caelyx or doxorubicin plus Tocilizumab
Intervention: Carboplatin and Caelyx or doxorubicin
Group 3
Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
Intervention: tocilizumab and interferon alpha 2-b
Group 3
Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
Intervention: Carboplatin and Caelyx or doxorubicin
Outcomes
Primary Outcomes
The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron
Time Frame: two years
The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured .
Secondary Outcomes
- The effect of chemo-immunotherapy on the immune system(two years)
- The relation between anti-tumor immunity and clinical outcome(two years)