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
PITCH
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.
1 other identifier
interventional
21
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Feb 2011
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2011
CompletedFirst Submitted
Initial submission to the registry
April 15, 2012
CompletedFirst Posted
Study publicly available on registry
July 11, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2013
CompletedJanuary 26, 2016
January 1, 2016
2.6 years
April 15, 2012
January 25, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
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
Secondary Outcomes (2)
The effect of chemo-immunotherapy on the immune system
two years
The relation between anti-tumor immunity and clinical outcome
two years
Study Arms (3)
Group 1
OTHERCarboplatin/Caelyx
Group 2
EXPERIMENTALCarboplatin/Caelyx or doxorubicin plus Tocilizumab
Group 3
EXPERIMENTALCarboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
Interventions
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
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
Eligibility Criteria
You may qualify if:
- 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
- x UNL (\<5x UNL in case of liver metastases), Alkaline Phosphatase ≤5 x UNL
- Adequate renal function: the calculated creatinine clearance should be
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Leiden University Medical Center
Leiden, 2333 ZA, Netherlands
Related Publications (1)
Dijkgraaf EM, Santegoets SJ, Reyners AK, Goedemans R, Wouters MC, Kenter GG, van Erkel AR, van Poelgeest MI, Nijman HW, van der Hoeven JJ, Welters MJ, van der Burg SH, Kroep JR. A phase I trial combining carboplatin/doxorubicin with tocilizumab, an anti-IL-6R monoclonal antibody, and interferon-alpha2b in patients with recurrent epithelial ovarian cancer. Ann Oncol. 2015 Oct;26(10):2141-9. doi: 10.1093/annonc/mdv309. Epub 2015 Jul 27.
PMID: 26216383DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
G Blecourt
LUMC
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- MD, PhD
Study Record Dates
First Submitted
April 15, 2012
First Posted
July 11, 2012
Study Start
February 1, 2011
Primary Completion
September 1, 2013
Study Completion
September 1, 2013
Last Updated
January 26, 2016
Record last verified: 2016-01