Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer

Phase 1

Completed

• Conditions: Recurrent Ovarian Cancer
• Interventions: Drug: Interferon Alfa-2b; Biological: p53 SLP

• Registration Number: NCT01639885
• Lead Sponsor: Leiden University Medical Center

Brief Summary

This study investigates the feasibility and immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination in patients with platinum-resistant ovarian cancer.

Detailed Description

Recurrent ovarian cancer has a dismal prognosis and there is a pressing need to identify more efficient therapies. Ovarian cancer is highly immunogenic and good survival is tightly linked to the presence of tumor-infiltrating T cells and the absence of immunosuppressive immune cells. This anti-tumor immune response might be primed by chemotherapy.

Gemcitabine has immune-modulatory properties in addition to its direct cytotoxic effect in platinum resistant ovarian cancer. Additionally, Peg-Intron allows the full maturation of dendritic cells, thereby enhancing the anti-tumor response. Moreover, the tumor-associated self-antigen p53 is commonly over-expressed in ovarian cancer and can serve as a target for immunotherapy. Therefore, chemo-immunotherapy with gemcitabine and Peg-Intron plus/minus p53 SLP vaccination seems an attractive treatment for recurrent, p53+ ovarian cancer patients.

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2012-04-16
• Study First Submitted QC: 2012-07-12
• Study First Posted: 2012-07-13
• Status Verified: 2014-01
• Primary Completion: 2014-01
• Last Update Submitted: 2014-01-06
• Last Update Posted: 2014-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 15

Inclusion Criteria

• Histological proven epithelial ovarian cancer, peritoneal cavity or fallopian tube cancer (inclusive mucinous or clear cell tumors)
• Tumor over-expressing p53
• Progression of disease or relapse after previous therapy with platinum
• Measurable disease (RECIST 1.1) or elevated CA125 > 2 times the upper limit of normal 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 upper limit of normal (UNL) range, ALAT and/or ASAT ≤ 2.5 x UNL, 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

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2	Interferon Alfa-2b	Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron)
Group 3	p53 SLP	Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin
Group 3	Interferon Alfa-2b	Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin

Primary Outcome Measures

Name	Time	Method
Feasibility (change in grade III and IV toxicity) and change in immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination	Before treatment, after 2 months and after 6 months after start therapy	During the trial we will measure the incidence and severity of all side effects (according to CTC version 4.0). The change in immunogenecity will be measured according to the induction of p53-specific T cells upon treatment.

Secondary Outcome Measures

Name	Time	Method
progression free survival	Before treatment, after 2 months and after 6 months after start therapy
overall survival	Before treatment, after 2 months and after 6 months after start therapy
Clinical outcome (response (RECIST 1.1)	Before treatment, after 2 months and after 6 months after start therapy	Clinical outcome will be tested by analyzing CA125 in sera and tumor size at CT (by RECIST 1.1)and time from start treatment until death
The effect of this new treatment combination on the immune system	Before treatment, after two months and after 6 months after treatment	Changes in plasma signature and tumor tissue will be measured

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands