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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)

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ClinicalTrials.gov Identifier: NCT01637532
Recruitment Status : Completed
First Posted : July 11, 2012
Last Update Posted : January 26, 2016
Sponsor:
Collaborator:
University Medical Center Groningen
Information provided by (Responsible Party):
J.R. Kroep, Leiden University Medical Center

Tracking Information
First Submitted Date  ICMJE April 15, 2012
First Posted Date  ICMJE July 11, 2012
Last Update Posted Date January 26, 2016
Study Start Date  ICMJE February 2011
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2012)
The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron [ Time Frame: two years ]
The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured .
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2012)
  • The effect of chemo-immunotherapy on the immune system [ Time Frame: two years ]
    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
  • The relation between anti-tumor immunity and clinical outcome [ Time Frame: two years ]
    Study the relation between anti-tumor immunity and clinical outcome (response (RECIST 1.1), progression free survival (PFS) and overall survival(OS))
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent Ovarian Cancer
Intervention  ICMJE
  • 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

  • Drug: Carboplatin and Caelyx or doxorubicin
    Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
Study Arms  ICMJE
  • Group 1
    Carboplatin/Caelyx
    Intervention: Drug: Carboplatin and Caelyx or doxorubicin
  • Experimental: Group 2
    Carboplatin/Caelyx or doxorubicin plus Tocilizumab
    Interventions:
    • Drug: tocilizumab and interferon alpha 2-b
    • Drug: Carboplatin and Caelyx or doxorubicin
  • Experimental: Group 3
    Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
    Interventions:
    • Drug: tocilizumab and interferon alpha 2-b
    • Drug: Carboplatin and Caelyx or doxorubicin
Publications * 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-α2b in patients with recurrent epithelial ovarian cancer. Ann Oncol. 2015 Oct;26(10):2141-9. doi: 10.1093/annonc/mdv309. Epub 2015 Jul 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2012)
21
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01637532
Other Study ID Numbers  ICMJE PITCH trial
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party J.R. Kroep, Leiden University Medical Center
Study Sponsor  ICMJE Leiden University Medical Center
Collaborators  ICMJE University Medical Center Groningen
Investigators  ICMJE
Study Director: G Blecourt LUMC
PRS Account Leiden University Medical Center
Verification Date January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP