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)

Leiden University Medical Center (LUMC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Recurrent Ovarian Cancer

Treatments: Drug: tocilizumab and interferon alpha 2-b; Drug: Carboplatin and Caelyx or doxorubicin

Study type: Interventional

Funder types: Other

Identifiers

NCT01637532

PITCH trial

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

21 participants in 3 patient groups

Group 1

Other group

Description:

Carboplatin/Caelyx

Treatment:

Drug: Carboplatin and Caelyx or doxorubicin

Group 2

Experimental group

Description:

Carboplatin/Caelyx or doxorubicin plus Tocilizumab

Treatment:

Drug: Carboplatin and Caelyx or doxorubicin

Drug: tocilizumab and interferon alpha 2-b

Group 3

Experimental group

Description:

Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron

Treatment:

Drug: Carboplatin and Caelyx or doxorubicin

Drug: tocilizumab and interferon alpha 2-b