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

NCT ID: NCT01637532

Last Updated: 2016-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2013-09-30

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.

Conditions

Recurrent Ovarian Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1

Carboplatin/Caelyx

Group Type: OTHER

Carboplatin and Caelyx or doxorubicin

Intervention Type: DRUG

Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.

Group 2

Carboplatin/Caelyx or doxorubicin plus Tocilizumab

Group Type: EXPERIMENTAL

tocilizumab and interferon alpha 2-b

Intervention Type: 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

Carboplatin and Caelyx or doxorubicin

Intervention Type: DRUG

Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.

Group 3

Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron

Group Type: EXPERIMENTAL

tocilizumab and interferon alpha 2-b

Intervention Type: 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

Carboplatin and Caelyx or doxorubicin

Intervention Type: DRUG

Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.

Interventions

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

Intervention Type: DRUG

Carboplatin and Caelyx or doxorubicin

Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

J.R. Kroep

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

G Blecourt

Role: STUDY_DIRECTOR

LUMC

Locations

Leiden University Medical Center

Leiden, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 26216383 (View on PubMed)

Other Identifiers

PITCH trial

Identifier Type: -

Identifier Source: org_study_id