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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)

Primary Purpose

Recurrent Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
tocilizumab and interferon alpha 2-b
Carboplatin and Caelyx or doxorubicin
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Leiden University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

Carboplatin/Caelyx

Carboplatin/Caelyx or doxorubicin plus Tocilizumab

Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron

Outcomes

Primary Outcome Measures

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 .

Secondary Outcome Measures

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
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))

Full Information

First Posted
April 15, 2012
Last Updated
January 25, 2016
Sponsor
Leiden University Medical Center
Collaborators
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT01637532
Brief Title
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
Acronym
PITCH
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

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center
Collaborators
University Medical Center Groningen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Ovarian Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Other
Arm Description
Carboplatin/Caelyx
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Carboplatin/Caelyx or doxorubicin plus Tocilizumab
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
Intervention Type
Drug
Intervention Name(s)
tocilizumab and interferon alpha 2-b
Intervention Description
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
Intervention Name(s)
Carboplatin and Caelyx or doxorubicin
Intervention Description
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
Primary Outcome Measure Information:
Title
The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron
Description
The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured .
Time Frame
two years
Secondary Outcome Measure Information:
Title
The effect of chemo-immunotherapy on the immune system
Description
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
Time Frame
two years
Title
The relation between anti-tumor immunity and clinical outcome
Description
Study the relation between anti-tumor immunity and clinical outcome (response (RECIST 1.1), progression free survival (PFS) and overall survival(OS))
Time Frame
two years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
G Blecourt
Organizational Affiliation
LUMC
Official's Role
Study Director
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
26216383
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.
Results Reference
derived

Learn more about this trial

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

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