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)

January 25, 2016 updated by: J.R. Kroep, Leiden University Medical Center

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Leiden, Netherlands, 2333 ZA
        • Leiden University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Group 1
Carboplatin/Caelyx
Drug: Carboplatin and Caelyx or doxorubicin
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
Experimental: Group 2
Carboplatin/Caelyx or doxorubicin plus Tocilizumab
Drug: Carboplatin and Caelyx or doxorubicin
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
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
Experimental: Group 3
Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
Drug: Carboplatin and Caelyx or doxorubicin
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
Time Frame: two years
The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured .
two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
two years
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))
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Collaborators

University Medical Center Groningen

Investigators

  • Study Director: G Blecourt, LUMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

April 15, 2012

First Submitted That Met QC Criteria

July 8, 2012

First Posted (Estimate)

July 11, 2012

Study Record Updates

Last Update Posted (Estimate)

January 26, 2016

Last Update Submitted That Met QC Criteria

January 25, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PITCH trial

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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