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

Recurrent Ovarian Cancer Clinical Trial

— PITCH  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01637532
• Other study ID #: PITCH trial
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 15, 2012
• Last updated: January 25, 2016
• Start date: February 2011
• Est. completion date: September 2013

Study information

• Verified date: January 2016
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Neoplasms
• Recurrent Ovarian Cancer

Intervention

Drug:
• tocilizumab 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
• Carboplatin and Caelyx or doxorubicin
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron	The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured .	two years	Yes
Secondary	The effect of chemo-immunotherapy on the immune system	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	two years	Yes
Secondary	The relation between anti-tumor immunity and clinical outcome	Study the relation between anti-tumor immunity and clinical outcome (response (RECIST 1.1), progression free survival (PFS) and overall survival(OS))	two years	Yes