Feasibility of the Combination of Chemotherapy (Carbo/Caelyx or Carbo/Doxorubicin) With Tocilizumab (mAb IL-6R) and Peg-Intron in Patients With Recurrent Ovarian Cancer

Phase 1

Completed

• Conditions: Recurrent Ovarian Cancer
• Interventions: Drug: tocilizumab and interferon alpha 2-b; Drug: Carboplatin and Caelyx or doxorubicin

• Registration Number: NCT01637532
• Lead Sponsor: Leiden University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2012-04-15
• Study First Submitted QC: 2012-07-08
• Study First Posted: 2012-07-11
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-25
• Last Update Posted: 2016-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 3	tocilizumab and interferon alpha 2-b	Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
Group 1	Carboplatin and Caelyx or doxorubicin	Carboplatin/Caelyx
Group 2	tocilizumab and interferon alpha 2-b	Carboplatin/Caelyx or doxorubicin plus Tocilizumab
Group 2	Carboplatin and Caelyx or doxorubicin	Carboplatin/Caelyx or doxorubicin plus Tocilizumab
Group 3	Carboplatin and Caelyx or doxorubicin	Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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))

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands