Clinical trial NCT01637532: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent Ovarian Cancer
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: University Medical Center Groningen
First posted: 2012-07-11
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* 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

Primary outcomes:
measure: The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron
timeFrame: two years
Secondary outcomes:
measure: The effect of chemo-immunotherapy on the immune system
timeFrame: two years
measure: The relation between anti-tumor immunity and clinical outcome
timeFrame: two years
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: LUMC
name: G Blecourt
role: STUDY_DIRECTOR
References:
citation: 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.