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)

This study has been completed.
Sponsor:
Collaborator:
University Medical Centre Groningen
Information provided by (Responsible Party):
J.R. Kroep, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01637532
First received: April 15, 2012
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Ovarian Cancer
Drug: tocilizumab and interferon alpha 2-b
Drug: Carboplatin and Caelyx or doxorubicin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

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 [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Study the relation between anti-tumor immunity and clinical outcome (response (RECIST 1.1), progression free survival (PFS) and overall survival(OS))


Enrollment: 21
Study Start Date: February 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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.
Experimental: Group 3
Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01637532

Locations
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2333 ZA
Sponsors and Collaborators
Leiden University Medical Center
University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: J.R. Kroep, MD, PhD, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01637532     History of Changes
Other Study ID Numbers: PITCH trial
Study First Received: April 15, 2012
Last Updated: January 6, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Liposomal doxorubicin
Carboplatin
Doxorubicin
Interferons
Peginterferon alfa-2b
Interferon-alpha
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014