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| Name | Class |
|---|---|
| University Medical Center Groningen | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Other | Carboplatin/Caelyx |
|
| Group 2 | Experimental | Carboplatin/Caelyx or doxorubicin plus Tocilizumab |
|
| Group 3 | Experimental | Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tocilizumab and interferon alpha 2-b | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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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
Adequate renal function: the calculated creatinine clearance should be
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:
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| Name | Affiliation | Role |
|---|---|---|
| G Blecourt | LUMC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leiden University Medical Center | Leiden | 2333 ZA | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26216383 | Derived | 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. |
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| Carboplatin and Caelyx or doxorubicin | Drug | Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim. |
|
| two years |
| 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 |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
| D016190 | Carboplatin |
| C506643 | liposomal doxorubicin |
| D004317 | Doxorubicin |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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